This document discusses various classes of antibacterial drugs and their mechanisms of action. It describes drugs that inhibit bacterial cell wall biosynthesis like beta-lactams (penicillins, cephalosporins, carbapenems), glycopeptides, and bacitracin. It also covers drugs that inhibit bacterial protein synthesis, including aminoglycosides and tetracyclines which bind the 30S ribosomal subunit, and macrolides, lincosamides, and chloramphenicol which bind the 50S subunit. The document provides details on the structures, spectra of activity, and modes of action of representative drugs in each class.
Pharmacology of Semi synthetic Penicillins Vijay Kevlani
This document discusses various types of beta-lactam antibiotics including penicillins. It describes semisynthetic penicillins which were developed to overcome limitations of penicillin G, including poor oral efficacy and susceptibility to penicillinase. Examples mentioned include phenoxymethylpenicillin, methicillin, and extended spectrum penicillins. It also discusses beta-lactamase inhibitors like clavulanic acid which are used in combination with antibiotics to overcome bacterial resistance.
Insulin and HGH production using rDNA technologyMrinal Vashisth
This document discusses the production of insulin and human growth hormone (HGH) using recombinant DNA technology. It describes how conventional methods of extracting these proteins from animal sources are expensive and can cause allergic reactions. Recombinant DNA methods involve isolating the genes for insulin and HGH and inserting them into organisms like E. coli to produce the proteins. For insulin, different methods include producing the A and B chains separately and joining them, or inserting the proinsulin sequence. Analog insulin production also modifies the amino acid sequence. HGH is important for growth and development, and its gene has been inserted into expression cassettes and cultivated in bioreactors. Pharming is also discussed as a method of producing proteins by
This document discusses cell wall inhibiting antibiotics, specifically penicillins and cephalosporins. It describes how these drugs interfere with bacterial cell wall synthesis by inactivating penicillin-binding proteins, inhibiting transpeptidation and causing cell lysis. Resistance mechanisms like beta-lactamase production and changes to penicillin-binding proteins are also summarized. The antibiotic classes covered include penicillins, cephalosporins, carbapenems, monobactams and vancomycin.
Antibiotics are chemical substances that kill or inhibit the growth of microorganisms. They can be classified based on their source (natural, semisynthetic, synthetic), spectrum of activity (broad or narrow), or mechanism of action. Common mechanisms include inhibition of cell wall synthesis, protein synthesis, nucleic acid synthesis, and cell membrane function. Examples provided include penicillins, cephalosporins, carbapenems, glycopeptides, aminoglycosides, macrolides, quinolones, sulfonamides, and metronidazole.
1. The Kirbybauer method is a disc diffusion test used to determine antibiotic sensitivity. Filter paper discs loaded with antibiotics are placed on inoculated agar and allowed to diffuse. The zone of inhibition around each disc indicates sensitivity.
2. Antibiotics can inhibit bacterial cell wall, protein, or nucleic acid synthesis. Examples are penicillins blocking cell wall synthesis and rifampicin inhibiting bacterial transcription.
3. Antimicrobial resistance arises via mutations altering drug targets, enzymatic drug inactivation, or preventing drug uptake. It spreads between bacteria horizontally via plasmids encoding resistance genes. Prudent antibiotic use helps slow resistance development.
Pharmacology of Semi synthetic Penicillins Vijay Kevlani
This document discusses various types of beta-lactam antibiotics including penicillins. It describes semisynthetic penicillins which were developed to overcome limitations of penicillin G, including poor oral efficacy and susceptibility to penicillinase. Examples mentioned include phenoxymethylpenicillin, methicillin, and extended spectrum penicillins. It also discusses beta-lactamase inhibitors like clavulanic acid which are used in combination with antibiotics to overcome bacterial resistance.
Insulin and HGH production using rDNA technologyMrinal Vashisth
This document discusses the production of insulin and human growth hormone (HGH) using recombinant DNA technology. It describes how conventional methods of extracting these proteins from animal sources are expensive and can cause allergic reactions. Recombinant DNA methods involve isolating the genes for insulin and HGH and inserting them into organisms like E. coli to produce the proteins. For insulin, different methods include producing the A and B chains separately and joining them, or inserting the proinsulin sequence. Analog insulin production also modifies the amino acid sequence. HGH is important for growth and development, and its gene has been inserted into expression cassettes and cultivated in bioreactors. Pharming is also discussed as a method of producing proteins by
This document discusses cell wall inhibiting antibiotics, specifically penicillins and cephalosporins. It describes how these drugs interfere with bacterial cell wall synthesis by inactivating penicillin-binding proteins, inhibiting transpeptidation and causing cell lysis. Resistance mechanisms like beta-lactamase production and changes to penicillin-binding proteins are also summarized. The antibiotic classes covered include penicillins, cephalosporins, carbapenems, monobactams and vancomycin.
Antibiotics are chemical substances that kill or inhibit the growth of microorganisms. They can be classified based on their source (natural, semisynthetic, synthetic), spectrum of activity (broad or narrow), or mechanism of action. Common mechanisms include inhibition of cell wall synthesis, protein synthesis, nucleic acid synthesis, and cell membrane function. Examples provided include penicillins, cephalosporins, carbapenems, glycopeptides, aminoglycosides, macrolides, quinolones, sulfonamides, and metronidazole.
1. The Kirbybauer method is a disc diffusion test used to determine antibiotic sensitivity. Filter paper discs loaded with antibiotics are placed on inoculated agar and allowed to diffuse. The zone of inhibition around each disc indicates sensitivity.
2. Antibiotics can inhibit bacterial cell wall, protein, or nucleic acid synthesis. Examples are penicillins blocking cell wall synthesis and rifampicin inhibiting bacterial transcription.
3. Antimicrobial resistance arises via mutations altering drug targets, enzymatic drug inactivation, or preventing drug uptake. It spreads between bacteria horizontally via plasmids encoding resistance genes. Prudent antibiotic use helps slow resistance development.
Antimicrobials include antibacterials, antivirals, antifungals, and antiparasitic agents that inhibit or kill microorganisms. The document discusses various classes of antibiotics including their mechanisms of action and production sources. It describes how antibiotics can be bacteriostatic or bactericidal and covers antibiotic resistance mechanisms like changes to permeability, enzyme production, or target sites. Methods for determining antibiotic sensitivity are outlined, including disk diffusion assays and dilution tests to categorize organisms as resistant, intermediate, or sensitive.
Cephalosporins & other β lactam antibiotics & cell wall destructorsFarazaJaved
This document summarizes cephalosporin antibiotics and other β-lactam antibiotics. It discusses the classes of cephalosporins including their history, mechanisms of action, generations, and examples within each generation. It also describes other β-lactam antibiotics such as monobactams, carbapenems, and β-lactamase inhibitors. Additionally, it covers non-β-lactam cell wall acting antibiotics including vancomycin, daptomycin, fosfomycin, polymyxins, and cycloserine. The document provides detailed information on commonly used antibiotics in each class.
1. Cephalosporins are a class of antibiotics that are structurally similar to penicillins and act by inhibiting bacterial cell wall synthesis. They are grouped into generations based on their spectrum of activity, with later generations having greater activity against gram-negative bacteria.
2. Vancomycin is a glycopeptide antibiotic used to treat infections caused by gram-positive bacteria, as it interferes with their cell wall formation. It remains effective against many resistant strains but vancomycin-resistant enterococci have emerged as a problem.
3. Both classes are administered parenterally and distributed well throughout the body except within cells. They are eliminated renally and require dosage adjustment in renal impairment to avoid
This document provides an overview of penicillin and cephalosporin antibiotics. It discusses their mechanisms of action, categories, pharmacokinetics, and adverse effects. Penicillins work by interfering with bacterial cell wall synthesis, while cephalosporins have a similar mode of action but tend to be more resistant to beta-lactamases. Both are categorized based on their spectra of activity and resistance properties. Their absorption, distribution, metabolism, and excretion are also reviewed. Common adverse effects include hypersensitivity reactions and diarrhea.
Cephalosporins are a class of beta-lactam antibiotics that are similar in structure and mechanism of action to penicillins. They work by binding to penicillin-binding proteins in bacteria to inhibit cell wall synthesis. While earlier generations have more gram-positive coverage, later generations have enhanced activity against gram-negative organisms. Common adverse effects are mild and include rash, gastrointestinal issues, and hypersensitivity reactions. Intravenous third-generation cephalosporins like ceftriaxone and cefotaxime are useful for treating various bacterial infections due to their activity against pathogens like Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli.
- Penicillins are a major class of antibiotics that were the first discovered from the mold Penicillium. They work by inhibiting the final step of bacterial cell wall synthesis through binding to penicillin-binding proteins. This disrupts cell wall formation and causes cell lysis.
- There are different generations/classes of penicillins that vary in their spectra of activity and resistance to bacterial beta-lactamases. Oral forms are absorbed from the gastrointestinal tract while injectable forms provide more sustained drug levels. Adverse effects include hypersensitivity reactions and gastrointestinal issues.
The document discusses evolving strategies in antibiotic discovery and development. It focuses on how chemical modification of natural product scaffolds through semi-synthesis has dominated antibiotic development and led to many successful drugs. However, rising drug resistance requires new innovations, like developing antibiotic adjuvants to preserve existing drugs or expanding chemical diversity through synthetic biology or new techniques to mine antibiotic-producing organisms. Understanding antibiotic chemical properties and harnessing both synthetic chemistry and natural product discovery will be important to address the growing need for new antibiotics.
This document summarizes various classes of antibiotics that act by inhibiting bacterial protein synthesis. It discusses tetracyclines, aminoglycosides, macrolides, ketolides, chloramphenicol, clindamycin and others. Each drug class is briefly described in terms of mechanism of action, antibacterial spectrum, pharmacokinetics and common adverse effects. The document provides an overview of major antibiotics that inhibit bacterial protein synthesis.
The document defines various terms related to antibiotics such as antimicrobials, bacteriostatic, bactericidal, and antibiotic resistance. It describes different types of antibiotics like narrow and broad spectrum and discusses minimum inhibitory concentration. It provides historical context on the discovery of penicillin and discusses the classification, mechanisms of action, uses, and development of resistance for penicillins and cephalosporins. [/SUMMARY]
This document discusses cell wall inhibitors, specifically penicillins, cephalosporins, and carbapenems. It describes their mechanisms of action as inhibiting bacterial cell wall synthesis, their spectra of activity against gram-positive and gram-negative bacteria, and important mechanisms of resistance including beta-lactamase production. Important adverse effects and pharmacokinetics are also summarized.
This document discusses the history and definitions of antibiotics and chemotherapeutic agents. It begins by defining antibiotics as chemical substances produced by microorganisms that inhibit other microorganisms at low concentrations. The document then summarizes the history of antibiotics, including the discoveries of Paul Ehrlich, Gerhard Domagk, Alexander Fleming, and Selman Waksman. It also outlines the ideal properties of antimicrobial drugs and describes various antibiotic mechanisms of action, including inhibition of protein synthesis, DNA/RNA synthesis, and cell wall synthesis. The clinical uses and susceptibility testing of antibiotics are briefly discussed.
This document provides an overview of antimicrobial drugs used to treat and prevent infections. It begins with objectives of reviewing key concepts of antimicrobial therapy. It then discusses mechanisms of action for different classes of antimicrobials including why antibiotics only target bacterial cells. The remainder of the document covers specific classes of antimicrobial drugs like beta-lactams, macrolides, and vancomycin. It provides details on indications, mechanisms of action, and important nursing considerations for each drug class.
The document discusses various aspects of antimicrobial drugs and antibiotic resistance. It defines key terms like antimicrobials, antibiotics, and describes different classes of antibiotics including their mechanisms of action and examples. It discusses factors that influence the effectiveness of antibiotics like spectrum of activity, toxicity and resistance development. It differentiates between acquired and intrinsic antibiotic resistance, and lists factors like overuse/misuse of drugs, poor infection control and inappropriate antibiotic usage as major causes of acquired antibiotic resistance.
This document discusses antibiotics and their properties. It describes how antibiotics are chemical substances produced by microorganisms that kill or inhibit pathogenic bacteria without harming host tissue. An ideal antibiotic should have broad-spectrum activity, be effective at low concentrations, kill bacteria rather than just inhibiting growth, selectively target pathogens, and not induce bacterial resistance. The document then discusses specific classes of antibiotics like tetracyclines, penicillins, and cephalosporins, outlining their mechanisms of action, properties, uses, and mechanisms of resistance.
This document discusses cell wall inhibitors, specifically penicillins and cephalosporins. It covers their mechanisms of action, which involve inhibiting bacterial cell wall synthesis. It describes their antimicrobial spectra against gram-positive and gram-negative bacteria. Resistance mechanisms like beta-lactamase production are also summarized. The pharmacokinetics of administration, distribution, and excretion of these drugs is covered. Finally, the document outlines some common adverse effects.
beta lactam antibiotics,aminoglycosides, quinolones and macrolide antibioticsmohammed muzammil
This document provides information on beta-lactam antibiotics (penicillins, cephalosporins, monobactams, carbapenems), aminoglycosides, and quinolones. It describes the classes of antibiotics, their mechanisms of action, which involve inhibiting bacterial cell wall synthesis or protein synthesis, and mechanisms of resistance. It also discusses specific examples within each class and their properties, indications, and side effects.
Penicillin and other beta-lactam antibiotics work by inhibiting the final step of bacterial cell wall synthesis (transpeptidation or cross-linkage). This exposes the cell membrane which is structurally less stable. They inactivate bacterial enzymes called penicillin-binding proteins that are involved in cell wall synthesis and maintenance of cell morphology. Cephalosporins have a similar mechanism of action, inhibiting cell wall synthesis and activating autolysin enzymes. Carbapenems have broad-spectrum activity and are resistant to beta-lactamases. Vancomycin inhibits cell wall synthesis by binding to the D-alanyl-D-alanine portion of peptidoglycan precursors.
Candidate young stellar objects in the S-cluster: Kinematic analysis of a sub...Sérgio Sacani
Context. The observation of several L-band emission sources in the S cluster has led to a rich discussion of their nature. However, a definitive answer to the classification of the dusty objects requires an explanation for the detection of compact Doppler-shifted Brγ emission. The ionized hydrogen in combination with the observation of mid-infrared L-band continuum emission suggests that most of these sources are embedded in a dusty envelope. These embedded sources are part of the S-cluster, and their relationship to the S-stars is still under debate. To date, the question of the origin of these two populations has been vague, although all explanations favor migration processes for the individual cluster members. Aims. This work revisits the S-cluster and its dusty members orbiting the supermassive black hole SgrA* on bound Keplerian orbits from a kinematic perspective. The aim is to explore the Keplerian parameters for patterns that might imply a nonrandom distribution of the sample. Additionally, various analytical aspects are considered to address the nature of the dusty sources. Methods. Based on the photometric analysis, we estimated the individual H−K and K−L colors for the source sample and compared the results to known cluster members. The classification revealed a noticeable contrast between the S-stars and the dusty sources. To fit the flux-density distribution, we utilized the radiative transfer code HYPERION and implemented a young stellar object Class I model. We obtained the position angle from the Keplerian fit results; additionally, we analyzed the distribution of the inclinations and the longitudes of the ascending node. Results. The colors of the dusty sources suggest a stellar nature consistent with the spectral energy distribution in the near and midinfrared domains. Furthermore, the evaporation timescales of dusty and gaseous clumps in the vicinity of SgrA* are much shorter ( 2yr) than the epochs covered by the observations (≈15yr). In addition to the strong evidence for the stellar classification of the D-sources, we also find a clear disk-like pattern following the arrangements of S-stars proposed in the literature. Furthermore, we find a global intrinsic inclination for all dusty sources of 60 ± 20◦, implying a common formation process. Conclusions. The pattern of the dusty sources manifested in the distribution of the position angles, inclinations, and longitudes of the ascending node strongly suggests two different scenarios: the main-sequence stars and the dusty stellar S-cluster sources share a common formation history or migrated with a similar formation channel in the vicinity of SgrA*. Alternatively, the gravitational influence of SgrA* in combination with a massive perturber, such as a putative intermediate mass black hole in the IRS 13 cluster, forces the dusty objects and S-stars to follow a particular orbital arrangement. Key words. stars: black holes– stars: formation– Galaxy: center– galaxies: star formation
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Similar to Mechanisms of Antibacterial Drugs _ Microbiology.pdf
Antimicrobials include antibacterials, antivirals, antifungals, and antiparasitic agents that inhibit or kill microorganisms. The document discusses various classes of antibiotics including their mechanisms of action and production sources. It describes how antibiotics can be bacteriostatic or bactericidal and covers antibiotic resistance mechanisms like changes to permeability, enzyme production, or target sites. Methods for determining antibiotic sensitivity are outlined, including disk diffusion assays and dilution tests to categorize organisms as resistant, intermediate, or sensitive.
Cephalosporins & other β lactam antibiotics & cell wall destructorsFarazaJaved
This document summarizes cephalosporin antibiotics and other β-lactam antibiotics. It discusses the classes of cephalosporins including their history, mechanisms of action, generations, and examples within each generation. It also describes other β-lactam antibiotics such as monobactams, carbapenems, and β-lactamase inhibitors. Additionally, it covers non-β-lactam cell wall acting antibiotics including vancomycin, daptomycin, fosfomycin, polymyxins, and cycloserine. The document provides detailed information on commonly used antibiotics in each class.
1. Cephalosporins are a class of antibiotics that are structurally similar to penicillins and act by inhibiting bacterial cell wall synthesis. They are grouped into generations based on their spectrum of activity, with later generations having greater activity against gram-negative bacteria.
2. Vancomycin is a glycopeptide antibiotic used to treat infections caused by gram-positive bacteria, as it interferes with their cell wall formation. It remains effective against many resistant strains but vancomycin-resistant enterococci have emerged as a problem.
3. Both classes are administered parenterally and distributed well throughout the body except within cells. They are eliminated renally and require dosage adjustment in renal impairment to avoid
This document provides an overview of penicillin and cephalosporin antibiotics. It discusses their mechanisms of action, categories, pharmacokinetics, and adverse effects. Penicillins work by interfering with bacterial cell wall synthesis, while cephalosporins have a similar mode of action but tend to be more resistant to beta-lactamases. Both are categorized based on their spectra of activity and resistance properties. Their absorption, distribution, metabolism, and excretion are also reviewed. Common adverse effects include hypersensitivity reactions and diarrhea.
Cephalosporins are a class of beta-lactam antibiotics that are similar in structure and mechanism of action to penicillins. They work by binding to penicillin-binding proteins in bacteria to inhibit cell wall synthesis. While earlier generations have more gram-positive coverage, later generations have enhanced activity against gram-negative organisms. Common adverse effects are mild and include rash, gastrointestinal issues, and hypersensitivity reactions. Intravenous third-generation cephalosporins like ceftriaxone and cefotaxime are useful for treating various bacterial infections due to their activity against pathogens like Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli.
- Penicillins are a major class of antibiotics that were the first discovered from the mold Penicillium. They work by inhibiting the final step of bacterial cell wall synthesis through binding to penicillin-binding proteins. This disrupts cell wall formation and causes cell lysis.
- There are different generations/classes of penicillins that vary in their spectra of activity and resistance to bacterial beta-lactamases. Oral forms are absorbed from the gastrointestinal tract while injectable forms provide more sustained drug levels. Adverse effects include hypersensitivity reactions and gastrointestinal issues.
The document discusses evolving strategies in antibiotic discovery and development. It focuses on how chemical modification of natural product scaffolds through semi-synthesis has dominated antibiotic development and led to many successful drugs. However, rising drug resistance requires new innovations, like developing antibiotic adjuvants to preserve existing drugs or expanding chemical diversity through synthetic biology or new techniques to mine antibiotic-producing organisms. Understanding antibiotic chemical properties and harnessing both synthetic chemistry and natural product discovery will be important to address the growing need for new antibiotics.
This document summarizes various classes of antibiotics that act by inhibiting bacterial protein synthesis. It discusses tetracyclines, aminoglycosides, macrolides, ketolides, chloramphenicol, clindamycin and others. Each drug class is briefly described in terms of mechanism of action, antibacterial spectrum, pharmacokinetics and common adverse effects. The document provides an overview of major antibiotics that inhibit bacterial protein synthesis.
The document defines various terms related to antibiotics such as antimicrobials, bacteriostatic, bactericidal, and antibiotic resistance. It describes different types of antibiotics like narrow and broad spectrum and discusses minimum inhibitory concentration. It provides historical context on the discovery of penicillin and discusses the classification, mechanisms of action, uses, and development of resistance for penicillins and cephalosporins. [/SUMMARY]
This document discusses cell wall inhibitors, specifically penicillins, cephalosporins, and carbapenems. It describes their mechanisms of action as inhibiting bacterial cell wall synthesis, their spectra of activity against gram-positive and gram-negative bacteria, and important mechanisms of resistance including beta-lactamase production. Important adverse effects and pharmacokinetics are also summarized.
This document discusses the history and definitions of antibiotics and chemotherapeutic agents. It begins by defining antibiotics as chemical substances produced by microorganisms that inhibit other microorganisms at low concentrations. The document then summarizes the history of antibiotics, including the discoveries of Paul Ehrlich, Gerhard Domagk, Alexander Fleming, and Selman Waksman. It also outlines the ideal properties of antimicrobial drugs and describes various antibiotic mechanisms of action, including inhibition of protein synthesis, DNA/RNA synthesis, and cell wall synthesis. The clinical uses and susceptibility testing of antibiotics are briefly discussed.
This document provides an overview of antimicrobial drugs used to treat and prevent infections. It begins with objectives of reviewing key concepts of antimicrobial therapy. It then discusses mechanisms of action for different classes of antimicrobials including why antibiotics only target bacterial cells. The remainder of the document covers specific classes of antimicrobial drugs like beta-lactams, macrolides, and vancomycin. It provides details on indications, mechanisms of action, and important nursing considerations for each drug class.
The document discusses various aspects of antimicrobial drugs and antibiotic resistance. It defines key terms like antimicrobials, antibiotics, and describes different classes of antibiotics including their mechanisms of action and examples. It discusses factors that influence the effectiveness of antibiotics like spectrum of activity, toxicity and resistance development. It differentiates between acquired and intrinsic antibiotic resistance, and lists factors like overuse/misuse of drugs, poor infection control and inappropriate antibiotic usage as major causes of acquired antibiotic resistance.
This document discusses antibiotics and their properties. It describes how antibiotics are chemical substances produced by microorganisms that kill or inhibit pathogenic bacteria without harming host tissue. An ideal antibiotic should have broad-spectrum activity, be effective at low concentrations, kill bacteria rather than just inhibiting growth, selectively target pathogens, and not induce bacterial resistance. The document then discusses specific classes of antibiotics like tetracyclines, penicillins, and cephalosporins, outlining their mechanisms of action, properties, uses, and mechanisms of resistance.
This document discusses cell wall inhibitors, specifically penicillins and cephalosporins. It covers their mechanisms of action, which involve inhibiting bacterial cell wall synthesis. It describes their antimicrobial spectra against gram-positive and gram-negative bacteria. Resistance mechanisms like beta-lactamase production are also summarized. The pharmacokinetics of administration, distribution, and excretion of these drugs is covered. Finally, the document outlines some common adverse effects.
beta lactam antibiotics,aminoglycosides, quinolones and macrolide antibioticsmohammed muzammil
This document provides information on beta-lactam antibiotics (penicillins, cephalosporins, monobactams, carbapenems), aminoglycosides, and quinolones. It describes the classes of antibiotics, their mechanisms of action, which involve inhibiting bacterial cell wall synthesis or protein synthesis, and mechanisms of resistance. It also discusses specific examples within each class and their properties, indications, and side effects.
Penicillin and other beta-lactam antibiotics work by inhibiting the final step of bacterial cell wall synthesis (transpeptidation or cross-linkage). This exposes the cell membrane which is structurally less stable. They inactivate bacterial enzymes called penicillin-binding proteins that are involved in cell wall synthesis and maintenance of cell morphology. Cephalosporins have a similar mechanism of action, inhibiting cell wall synthesis and activating autolysin enzymes. Carbapenems have broad-spectrum activity and are resistant to beta-lactamases. Vancomycin inhibits cell wall synthesis by binding to the D-alanyl-D-alanine portion of peptidoglycan precursors.
Similar to Mechanisms of Antibacterial Drugs _ Microbiology.pdf (20)
Candidate young stellar objects in the S-cluster: Kinematic analysis of a sub...Sérgio Sacani
Context. The observation of several L-band emission sources in the S cluster has led to a rich discussion of their nature. However, a definitive answer to the classification of the dusty objects requires an explanation for the detection of compact Doppler-shifted Brγ emission. The ionized hydrogen in combination with the observation of mid-infrared L-band continuum emission suggests that most of these sources are embedded in a dusty envelope. These embedded sources are part of the S-cluster, and their relationship to the S-stars is still under debate. To date, the question of the origin of these two populations has been vague, although all explanations favor migration processes for the individual cluster members. Aims. This work revisits the S-cluster and its dusty members orbiting the supermassive black hole SgrA* on bound Keplerian orbits from a kinematic perspective. The aim is to explore the Keplerian parameters for patterns that might imply a nonrandom distribution of the sample. Additionally, various analytical aspects are considered to address the nature of the dusty sources. Methods. Based on the photometric analysis, we estimated the individual H−K and K−L colors for the source sample and compared the results to known cluster members. The classification revealed a noticeable contrast between the S-stars and the dusty sources. To fit the flux-density distribution, we utilized the radiative transfer code HYPERION and implemented a young stellar object Class I model. We obtained the position angle from the Keplerian fit results; additionally, we analyzed the distribution of the inclinations and the longitudes of the ascending node. Results. The colors of the dusty sources suggest a stellar nature consistent with the spectral energy distribution in the near and midinfrared domains. Furthermore, the evaporation timescales of dusty and gaseous clumps in the vicinity of SgrA* are much shorter ( 2yr) than the epochs covered by the observations (≈15yr). In addition to the strong evidence for the stellar classification of the D-sources, we also find a clear disk-like pattern following the arrangements of S-stars proposed in the literature. Furthermore, we find a global intrinsic inclination for all dusty sources of 60 ± 20◦, implying a common formation process. Conclusions. The pattern of the dusty sources manifested in the distribution of the position angles, inclinations, and longitudes of the ascending node strongly suggests two different scenarios: the main-sequence stars and the dusty stellar S-cluster sources share a common formation history or migrated with a similar formation channel in the vicinity of SgrA*. Alternatively, the gravitational influence of SgrA* in combination with a massive perturber, such as a putative intermediate mass black hole in the IRS 13 cluster, forces the dusty objects and S-stars to follow a particular orbital arrangement. Key words. stars: black holes– stars: formation– Galaxy: center– galaxies: star formation
Anti-Universe And Emergent Gravity and the Dark UniverseSérgio Sacani
Recent theoretical progress indicates that spacetime and gravity emerge together from the entanglement structure of an underlying microscopic theory. These ideas are best understood in Anti-de Sitter space, where they rely on the area law for entanglement entropy. The extension to de Sitter space requires taking into account the entropy and temperature associated with the cosmological horizon. Using insights from string theory, black hole physics and quantum information theory we argue that the positive dark energy leads to a thermal volume law contribution to the entropy that overtakes the area law precisely at the cosmological horizon. Due to the competition between area and volume law entanglement the microscopic de Sitter states do not thermalise at sub-Hubble scales: they exhibit memory effects in the form of an entropy displacement caused by matter. The emergent laws of gravity contain an additional ‘dark’ gravitational force describing the ‘elastic’ response due to the entropy displacement. We derive an estimate of the strength of this extra force in terms of the baryonic mass, Newton’s constant and the Hubble acceleration scale a0 = cH0, and provide evidence for the fact that this additional ‘dark gravity force’ explains the observed phenomena in galaxies and clusters currently attributed to dark matter.
Microbial interaction
Microorganisms interacts with each other and can be physically associated with another organisms in a variety of ways.
One organism can be located on the surface of another organism as an ectobiont or located within another organism as endobiont.
Microbial interaction may be positive such as mutualism, proto-cooperation, commensalism or may be negative such as parasitism, predation or competition
Types of microbial interaction
Positive interaction: mutualism, proto-cooperation, commensalism
Negative interaction: Ammensalism (antagonism), parasitism, predation, competition
I. Mutualism:
It is defined as the relationship in which each organism in interaction gets benefits from association. It is an obligatory relationship in which mutualist and host are metabolically dependent on each other.
Mutualistic relationship is very specific where one member of association cannot be replaced by another species.
Mutualism require close physical contact between interacting organisms.
Relationship of mutualism allows organisms to exist in habitat that could not occupied by either species alone.
Mutualistic relationship between organisms allows them to act as a single organism.
Examples of mutualism:
i. Lichens:
Lichens are excellent example of mutualism.
They are the association of specific fungi and certain genus of algae. In lichen, fungal partner is called mycobiont and algal partner is called
II. Syntrophism:
It is an association in which the growth of one organism either depends on or improved by the substrate provided by another organism.
In syntrophism both organism in association gets benefits.
Compound A
Utilized by population 1
Compound B
Utilized by population 2
Compound C
utilized by both Population 1+2
Products
In this theoretical example of syntrophism, population 1 is able to utilize and metabolize compound A, forming compound B but cannot metabolize beyond compound B without co-operation of population 2. Population 2is unable to utilize compound A but it can metabolize compound B forming compound C. Then both population 1 and 2 are able to carry out metabolic reaction which leads to formation of end product that neither population could produce alone.
Examples of syntrophism:
i. Methanogenic ecosystem in sludge digester
Methane produced by methanogenic bacteria depends upon interspecies hydrogen transfer by other fermentative bacteria.
Anaerobic fermentative bacteria generate CO2 and H2 utilizing carbohydrates which is then utilized by methanogenic bacteria (Methanobacter) to produce methane.
ii. Lactobacillus arobinosus and Enterococcus faecalis:
In the minimal media, Lactobacillus arobinosus and Enterococcus faecalis are able to grow together but not alone.
The synergistic relationship between E. faecalis and L. arobinosus occurs in which E. faecalis require folic acid
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
ESA/ACT Science Coffee: Diego Blas - Gravitational wave detection with orbita...Advanced-Concepts-Team
Presentation in the Science Coffee of the Advanced Concepts Team of the European Space Agency on the 07.06.2024.
Speaker: Diego Blas (IFAE/ICREA)
Title: Gravitational wave detection with orbital motion of Moon and artificial
Abstract:
In this talk I will describe some recent ideas to find gravitational waves from supermassive black holes or of primordial origin by studying their secular effect on the orbital motion of the Moon or satellites that are laser ranged.
PPT on Alternate Wetting and Drying presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
Mending Clothing to Support Sustainable Fashion_CIMaR 2024.pdfSelcen Ozturkcan
Ozturkcan, S., Berndt, A., & Angelakis, A. (2024). Mending clothing to support sustainable fashion. Presented at the 31st Annual Conference by the Consortium for International Marketing Research (CIMaR), 10-13 Jun 2024, University of Gävle, Sweden.
SDSS1335+0728: The awakening of a ∼ 106M⊙ black hole⋆Sérgio Sacani
Context. The early-type galaxy SDSS J133519.91+072807.4 (hereafter SDSS1335+0728), which had exhibited no prior optical variations during the preceding two decades, began showing significant nuclear variability in the Zwicky Transient Facility (ZTF) alert stream from December 2019 (as ZTF19acnskyy). This variability behaviour, coupled with the host-galaxy properties, suggests that SDSS1335+0728 hosts a ∼ 106M⊙ black hole (BH) that is currently in the process of ‘turning on’. Aims. We present a multi-wavelength photometric analysis and spectroscopic follow-up performed with the aim of better understanding the origin of the nuclear variations detected in SDSS1335+0728. Methods. We used archival photometry (from WISE, 2MASS, SDSS, GALEX, eROSITA) and spectroscopic data (from SDSS and LAMOST) to study the state of SDSS1335+0728 prior to December 2019, and new observations from Swift, SOAR/Goodman, VLT/X-shooter, and Keck/LRIS taken after its turn-on to characterise its current state. We analysed the variability of SDSS1335+0728 in the X-ray/UV/optical/mid-infrared range, modelled its spectral energy distribution prior to and after December 2019, and studied the evolution of its UV/optical spectra. Results. From our multi-wavelength photometric analysis, we find that: (a) since 2021, the UV flux (from Swift/UVOT observations) is four times brighter than the flux reported by GALEX in 2004; (b) since June 2022, the mid-infrared flux has risen more than two times, and the W1−W2 WISE colour has become redder; and (c) since February 2024, the source has begun showing X-ray emission. From our spectroscopic follow-up, we see that (i) the narrow emission line ratios are now consistent with a more energetic ionising continuum; (ii) broad emission lines are not detected; and (iii) the [OIII] line increased its flux ∼ 3.6 years after the first ZTF alert, which implies a relatively compact narrow-line-emitting region. Conclusions. We conclude that the variations observed in SDSS1335+0728 could be either explained by a ∼ 106M⊙ AGN that is just turning on or by an exotic tidal disruption event (TDE). If the former is true, SDSS1335+0728 is one of the strongest cases of an AGNobserved in the process of activating. If the latter were found to be the case, it would correspond to the longest and faintest TDE ever observed (or another class of still unknown nuclear transient). Future observations of SDSS1335+0728 are crucial to further understand its behaviour. Key words. galaxies: active– accretion, accretion discs– galaxies: individual: SDSS J133519.91+072807.4
2. LEARNING OBJECTIVES
Describe the mechanisms of action associated with drugs that inhibit cell
wall biosynthesis, protein synthesis, membrane function, nucleic acid
synthesis, and metabolic pathways
An important quality for an antimicrobial drug is selective toxicity, meaning that it selectively
kills or inhibits the growth of microbial targets while causing minimal or no harm to the host.
Most antimicrobial drugs currently in clinical use are antibacterial because the prokaryotic
cell provides a greater variety of unique targets for selective toxicity, in comparison to fungi,
parasites, and viruses. Each class of antibacterial drugs has a unique mode of action (the
way in which a drug a ects microbes at the cellular level), and these are summarized in
Figure 1 and Table 1.
Figure 1. There are several classes of antibacterial compounds that are typically classi ed based
on their bacterial target.
3. Table 1. Common Antibacterial Drugs by Mode of Action
Mode of Action Target Drug Class
Inhibit cell wall biosynthesis
Penicillin-binding
proteins
β-lactams: penicillins,
cephalosporins, monobactams,
carbapenems
Peptidoglycan subunits Glycopeptides
Peptidoglycan subunit
transport
Bacitracin
Inhibit biosynthesis of proteins
30S ribosomal subunit Aminoglycosides, tetracyclines
50S ribosomal subunit
Macrolides, lincosamides,
chloramphenicol, oxazolidinones
Disrupt membranes
Lipopolysaccharide,
inner and outer
membranes
Polymyxin B, colistin, daptomycin
Inhibit nucleic acid synthesis
RNA Rifamycin
DNA Fluoroquinolones
Antimetabolites
Folic acid synthesis
enzyme
Sulfonamides, trimethoprim
Mycolic acid synthesis
enzyme
Isonicotinic acid hydrazide
Mycobacterial adenosine
triphosphate (ATP) synthase
inhibitor
Mycobacterial ATP
synthase
Diarylquinoline
Inhibitors of Cell Wall Biosynthesis
Several di erent classes of antibacterials block steps in the biosynthesis of peptidoglycan,
making cells more susceptible to osmotic lysis (Table 2). Therefore, antibacterials that target
cell wall biosynthesis are bactericidal in their action. Because human cells do not make
peptidoglycan, this mode of action is an excellent example of selective toxicity.
4. Table 2. Drugs that Inhibit Bacterial Cell Wall Synthesis
Mechanism of
Action
Drug Class Speci c Drugs
Natural or
Semisynthetic
Spectrum of
Activity
Interact directly with
PBPs and inhibit
transpeptidase
activity
Penicillins
Penicillin G,
penicillin V
Natural
Narrow-
spectrum
against gram-
positive and a
few gram-
negative
bacteria
Ampicillin,
amoxicillin
Semisynthetic
Narrow-
spectrum
against gram-
positive
bacteria but
with
increased
gram-
negative
spectrum
Methicillin Semisynthetic
Narrow-
spectrum
against gram-
positive
bacteria only,
including
strains
producing
penicillinase
Cephalosporins
Cephalosporin
C
Natural
Narrow-
spectrum
similar to
penicillin but
with
increased
gram-
negative
spectrum
First-
generation
cephalosporins
Semisynthetic
Narrow-
spectrum
similar to
cephalosporin
C
5. Table 2. Drugs that Inhibit Bacterial Cell Wall Synthesis
Mechanism of
Action
Drug Class Speci c Drugs
Natural or
Semisynthetic
Spectrum of
Activity
Second-
generation
cephalosporins
Semisynthetic
Narrow-
spectrum but
with
increased
gram-
negative
spectrum
compared
with rst
generation
Third- and
fourth-
generation
cephalosporins
Semisynthetic
Broad-
spectrum
against gram-
positive and
gram-
negative
bacteria,
including
some β-
lactamase
producers
Fifth-
generation
cephalosporins
Semisynthetic
Broad-
spectrum
against gram-
positive and
gram-
negative
bacteria,
including
MRSA
Monobactams Aztreonam Semisynthetic
Narrow-
spectrum
against gram-
negative
bacteria,
including
some β-
lactamase
producers
6. Table 2. Drugs that Inhibit Bacterial Cell Wall Synthesis
Mechanism of
Action
Drug Class Speci c Drugs
Natural or
Semisynthetic
Spectrum of
Activity
Carbapenems
Imipenem,
meropenem,
doripenem
Semisynthetic
Broadest
spectrum of
the β-lactams
against gram-
positive and
gram-
negative
bacteria,
including
many β-
lactamase
producers
Large molecules
that bind to the
peptide chain of
peptidoglycan
subunits, blocking
transglycosylation
and
transpeptidation
Glycopeptides Vancomycin Natural
Narrow
spectrum
against gram-
positive
bacteria only,
including
multidrug-
resistant
strains
Block transport of
peptidoglycan
subunits across
cytoplasmic
membrane
Bacitracin Bacitracin Natural
Broad-
spectrum
against gram-
positive and
gram-
negative
bacteria
Penicillin, the rst antibiotic discovered, is one of several antibacterials within a class called
β-lactams. This group of compounds includes the penicillins, cephalosporins,
monobactams, and carbapenems, and is characterized by the presence of a β-lactam ring
found within the central structure of the drug molecule (Figure 2). The β-lactam antibacterials
block the crosslinking of peptide chains during the biosynthesis of new peptidoglycan in the
bacterial cell wall. They are able to block this process because the β-lactam structure is
similar to the structure of the peptidoglycan subunit component that is recognized by the
crosslinking transpeptidase enzyme, also known as a penicillin-binding protein (PBP).
Although the β-lactam ring must remain unchanged for these drugs to retain their
antibacterial activity, strategic chemical changes to the R groups have allowed for
development of a wide variety of semisynthetic β-lactam drugs with increased potency,
expanded spectrum of activity, and longer half-lives for better dosing, among other
characteristics.
Penicillin G and penicillin V are natural antibiotics from fungi and are primarily active against
gram-positive bacterial pathogens, and a few gram-negative bacterial pathogens such as
7. Pasteurella multocida. Figure 2 summarizes the semisynthetic development of some of the
penicillins. Adding an amino group (−NH2) to penicillin G created the aminopenicillins (i.e.,
ampicillin and amoxicillin) that have increased spectrum of activity against more gram-
negative pathogens. Furthermore, the addition of a hydroxyl group (−OH) to amoxicillin
increased acid stability, which allows for improved oral absorption. Methicillin is a
semisynthetic penicillin that was developed to address the spread of enzymes
(penicillinases) that were inactivating the other penicillins. Changing the R group of
penicillin G to the more bulky dimethoxyphenyl group provided protection of the β-lactam
ring from enzymatic destruction by penicillinases, giving us the rst penicillinase-resistant
penicillin.
Similar to the penicillins, cephalosporins contain a β-lactam ring (Figure 2) and block the
transpeptidase activity of penicillin-binding proteins. However, the β-lactam ring of
cephalosporins is fused to a six-member ring, rather than the ve-member ring found in
penicillins. This chemical di erence provides cephalosporins with an increased resistance to
enzymatic inactivation by β-lactamases. The drug cephalosporin C was originally isolated
from the fungus Cephalosporium acremonium in the 1950s and has a similar spectrum of
activity to that of penicillin against gram-positive bacteria but is active against more gram-
negative bacteria than penicillin. Another important structural di erence is that
cephalosporin C possesses two R groups, compared with just one R group for penicillin, and
this provides for greater diversity in chemical alterations and development of semisynthetic
cephalosporins. The family of semisynthetic cephalosporins is much larger than the
penicillins, and these drugs have been classi ed into generations based primarily on their
spectrum of activity, increasing in spectrum from the narrow-spectrum, rst-generation
cephalosporins to the broad-spectrum, fourth-generation cephalosporins. A new fth-
generation cephalosporin has been developed that is active against methicillin-resistant
Staphylococcus aureus (MRSA).
8. Figure 2. Penicillins, cephalosporins, monobactams, and carbapenems all contain a β-lactam ring,
the site of attack by inactivating β-lactamase enzymes. Although they all share the same nucleus,
various penicillins di er from each other in the structure of their R groups. Chemical changes to
the R groups provided increased spectrum of activity, acid stability, and resistance to β-lactamase
degradation.
The carbapenems and monobactams also have a β-lactam ring as part of their core
structure, and they inhibit the transpeptidase activity of penicillin-binding proteins. The only
monobactam used clinically is aztreonam. It is a narrow-spectrum antibacterial with activity
only against gram-negative bacteria. In contrast, the carbapenem family includes a variety of
semisynthetic drugs (imipenem, meropenem, and doripenem) that provide very broad-
spectrum activity against gram-positive and gram-negative bacterial pathogens.
The drug vancomycin, a member of a class of compounds called the glycopeptides, was
discovered in the 1950s as a natural antibiotic from the actinomycete Amycolatopsis
orientalis. Similar to the β-lactams, vancomycin inhibits cell wall biosynthesis and is
bactericidal. However, in contrast to the β-lactams, the structure of vancomycin is not similar
to that of cell-wall peptidoglycan subunits and does not directly inactivate penicillin-binding
proteins. Rather, vancomycin is a very large, complex molecule that binds to the end of the
peptide chain of cell wall precursors, creating a structural blockage that prevents the cell
wall subunits from being incorporated into the growing N-acetylglucosamine and N-
acetylmuramic acid (NAM-NAG) backbone of the peptidoglycan structure
(transglycosylation). Vancomycin also structurally blocks transpeptidation. Vancomycin is
bactericidal against gram-positive bacterial pathogens, but it is not active against gram-
negative bacteria because of its inability to penetrate the protective outer membrane.
9. The drug bacitracin consists of a group of structurally similar peptide antibiotics originally
isolated from Bacillus subtilis. Bacitracin blocks the activity of a speci c cell-membrane
molecule that is responsible for the movement of peptidoglycan precursors from the
cytoplasm to the exterior of the cell, ultimately preventing their incorporation into the cell
wall. Bacitracin is e ective against a wide range of bacteria, including gram-positive
organisms found on the skin, such as Staphylococcus and Streptococcus. Although it may
be administered orally or intramuscularly in some circumstances, bacitracin has been shown
to be nephrotoxic (damaging to the kidneys). Therefore, it is more commonly combined with
neomycin and polymyxin in topical ointments such as Neosporin.
THINK ABOUT IT
Describe the mode of action of β-lactams.
Inhibitors of Protein Biosynthesis
The cytoplasmic ribosomes found in animal cells (80S) are structurally distinct from those
found in bacterial cells (70S), making protein biosynthesis a good selective target for
antibacterial drugs. Several types of protein biosynthesis inhibitors are discussed in this
section and are summarized in Figure 3.
Figure 3. The major classes of protein synthesis inhibitors target the 30S or 50S subunits of
cytoplasmic ribosomes.
10. Protein Synthesis Inhibitors That Bind the 30S Subunit
Aminoglycosides are large, highly polar antibacterial drugs that bind to the 30S subunit of
bacterial ribosomes, impairing the proofreading ability of the ribosomal complex. This
impairment causes mismatches between codons and anticodons, resulting in the production
of proteins with incorrect amino acids and shortened proteins that insert into the cytoplasmic
membrane. Disruption of the cytoplasmic membrane by the faulty proteins kills the bacterial
cells. The aminoglycosides, which include drugs such as streptomycin, gentamicin,
neomycin, and kanamycin, are potent broad-spectrum antibacterials. However,
aminoglycosides have been shown to be nephrotoxic (damaging to kidney), neurotoxic
(damaging to the nervous system), and ototoxic (damaging to the ear).
Another class of antibacterial compounds that bind to the 30S subunit is the tetracyclines. In
contrast to aminoglycosides, these drugs are bacteriostatic and inhibit protein synthesis by
blocking the association of tRNAs with the ribosome during translation. Naturally occurring
tetracyclines produced by various strains of Streptomyces were rst discovered in the
1940s, and several semisynthetic tetracyclines, including doxycycline and tigecycline have
also been produced. Although the tetracyclines are broad spectrum in their coverage of
bacterial pathogens, side e ects that can limit their use include phototoxicity, permanent
discoloration of developing teeth, and liver toxicity with high doses or in patients with kidney
impairment.
Protein Synthesis Inhibitors That Bind the 50S Subunit
There are several classes of antibacterial drugs that work through binding to the 50S
subunit of bacterial ribosomes. The macrolide antibacterial drugs have a large, complex ring
structure and are part of a larger class of naturally produced secondary metabolites called
polyketides, complex compounds produced in a stepwise fashion through the repeated
addition of two-carbon units by a mechanism similar to that used for fatty acid synthesis.
Macrolides are broad-spectrum, bacteriostatic drugs that block elongation of proteins by
inhibiting peptide bond formation between speci c combinations of amino acids. The rst
macrolide was erythromycin. It was isolated in 1952 from Streptomyces erythreus and
prevents translocation. Semisynthetic macrolides include azithromycin and telithromycin.
Compared with erythromycin, azithromycin has a broader spectrum of activity, fewer side
e ects, and a signi cantly longer half-life (1.5 hours for erythromycin versus 68 hours for
azithromycin) that allows for once-daily dosing and a short 3-day course of therapy (i.e., Zpac
formulation) for most infections. Telithromycin is the rst semisynthetic within the class
known as ketolides. Although telithromycin shows increased potency and activity against
macrolide-resistant pathogens, the US Food and Drug Administration (FDA) has limited its
use to treatment of community-acquired pneumonia and requires the strongest “black box
warning” label for the drug because of serious hepatotoxicity.
11. The lincosamides include the naturally produced lincomycin and semisynthetic
clindamycin. Although structurally distinct from macrolides, lincosamides are similar in their
mode of action to the macrolides through binding to the 50S ribosomal subunit and
preventing peptide bond formation. Lincosamides are particularly active against
streptococcal and staphylococcal infections.
The drug chloramphenicol represents yet another structurally distinct class of antibacterials
that also bind to the 50S ribosome, inhibiting peptide bond formation. Chloramphenicol,
produced by Streptomyces venezuelae, was discovered in 1947; in 1949, it became the rst
broad-spectrum antibiotic that was approved by the FDA. Although it is a natural antibiotic, it
is also easily synthesized and was the rst antibacterial drug synthetically mass produced.
As a result of its mass production, broad-spectrum coverage, and ability to penetrate into
tissues e ciently, chloramphenicol was historically used to treat a wide range of infections,
from meningitis to typhoid fever to conjunctivitis. Unfortunately, serious side e ects, such
as lethal gray baby syndrome, and suppression of bone marrow production, have limited its
clinical role. Chloramphenicol also causes anemia in two di erent ways. One mechanism
involves the targeting of mitochondrial ribosomes within hematopoietic stem cells, causing a
reversible, dose-dependent suppression of blood cell production. Once chloramphenicol
dosing is discontinued, blood cell production returns to normal. This mechanism highlights
the similarity between 70S ribosomes of bacteria and the 70S ribosomes within our
mitochondria. The second mechanism of anemia is idiosyncratic (i.e., the mechanism is not
understood), and involves an irreversible lethal loss of blood cell production known as
aplastic anemia. This mechanism of aplastic anemia is not dose dependent and can
develop after therapy has stopped. Because of toxicity concerns, chloramphenicol usage in
humans is now rare in the United States and is limited to severe infections unable to be
treated by less toxic antibiotics. Because its side e ects are much less severe in animals, it is
used in veterinary medicine.
The oxazolidinones, including linezolid, are a new broad-spectrum class of synthetic protein
synthesis inhibitors that bind to the 50S ribosomal subunit of both gram-positive and gram-
negative bacteria. However, their mechanism of action seems somewhat di erent from that
of the other 50S subunit-binding protein synthesis inhibitors already discussed. Instead, they
seem to interfere with formation of the initiation complex (association of the 50S subunit,
30S subunit, and other factors) for translation, and they prevent translocation of the growing
protein from the ribosomal A site to the P site. Table 3 summarizes the protein synthesis
inhibitors.
12. Table 3. Drugs That Inhibit Bacterial Protein Synthesis
Molecular
Target
Mechanism
of Action
Drug Class Speci c Drugs
Bacteriostatic
or
Bactericidal
Spectrum
of
Activity
30S
subunit
Causes
mismatches
between
codons and
anticodons,
leading to
faulty
proteins
that insert
into and
disrupt
cytoplasmic
membrane
Aminoglycosides
Streptomycin,
gentamicin,
neomycin,
kanamycin
Bactericidal
Broad
spectrum
Blocks
association
of tRNAs
with
ribosome
Tetracyclines
Tetracycline,
doxycycline,
tigecycline
Bacteriostatic
Broad
spectrum
50S
subunit
Blocks
peptide
bond
formation
between
amino
acids
Macrolides
Erythromycin,
azithromycin,
telithromycin
Bacteriostatic
Broad
spectrum
Lincosamides
Lincomycin,
clindamycin
Bacteriostatic
Narrow
spectrum
Not applicable Chloramphenicol Bacteriostatic
Broad
spectrum
Interferes
with the
formation
of the
initiation
complex
between
50S and
30S
subunits
and other
factors.
Oxazolidinones Linezolid Bacteriostatic
Broad
spectrum
THINK ABOUT IT
Compare and contrast the di erent types of protein synthesis inhibitors.
13. Inhibitors of Membrane Function
A small group of antibacterials target the bacterial membrane as their mode of action (Table
4). The polymyxins are natural polypeptide antibiotics that were rst discovered in 1947 as
products of Bacillus polymyxa; only polymyxin B and polymyxin E (colistin) have been used
clinically. They are lipophilic with detergent-like properties and interact with the
lipopolysaccharide component of the outer membrane of gram-negative bacteria, ultimately
disrupting both their outer and inner membranes and killing the bacterial cells.
Unfortunately, the membrane-targeting mechanism is not a selective toxicity, and these
drugs also target and damage the membrane of cells in the kidney and nervous system
when administered systemically. Because of these serious side e ects and their poor
absorption from the digestive tract, polymyxin B is used in over-the-counter topical antibiotic
ointments (e.g., Neosporin), and oral colistin was historically used only for bowel
decontamination to prevent infections originating from bowel microbes in
immunocompromised patients or for those undergoing certain abdominal surgeries.
However, the emergence and spread of multidrug-resistant pathogens has led to increased
use of intravenous colistin in hospitals, often as a drug of last resort to treat serious
infections. The antibacterial daptomycin is a cyclic lipopeptide produced by Streptomyces
roseosporus that seems to work like the polymyxins, inserting in the bacterial cell
membrane and disrupting it. However, in contrast to polymyxin B and colistin, which target
only gram-negative bacteria, daptomycin speci cally targets gram-positive bacteria. It is
typically administered intravenously and seems to be well tolerated, showing reversible
toxicity in skeletal muscles.
14. Table 4. Drugs That Inhibit Bacterial Membrane Function
Mechanism of Action Drug Class
Speci c
Drugs
Spectrum
of
Activity
Clinical Use
Interacts with
lipopolysaccharide in
the outer membrane of
gram-negative bacteria,
killing the cell through
the eventual disruption
of the outer membrane
and cytoplasmic
membrane
Polymyxins
Polymyxin
B
Narrow
spectrum
against
gram-
negative
bacteria,
including
multidrug-
resistant
strains
Topical preparations
to prevent infections
in wounds
Polymyxin E
(colistin)
Narrow
spectrum
against
gram-
negative
bacteria,
including
multidrug-
resistant
strains
Oral dosing to
decontaminate
bowels to prevent
infections in
immunocompromised
patients or patients
undergoing invasive
surgery/procedures.
Intravenous dosing to
treat serious systemic
infections caused by
multidrug-resistant
pathogens
Inserts into the
cytoplasmic membrane
of gram-positive
bacteria, disrupting the
membrane and killing
the cell
Lipopeptide Daptomycin
Narrow
spectrum
against
gram-
positive
bacteria,
including
multidrug-
resistant
strains
Complicated skin and
skin-structure
infections and
bacteremia caused
by gram-positive
pathogens, including
MRSA
THINK ABOUT IT
How do polymyxins inhibit membrane function?
Inhibitors of Nucleic Acid Synthesis
Some antibacterial drugs work by inhibiting nucleic acid synthesis (Table 5). For example,
metronidazole is a semisynthetic member of the nitroimidazole family that is also an
15. antiprotozoan. It interferes with DNA replication in target cells. The drug rifampin is a
semisynthetic member of the rifamycin family and functions by blocking RNA polymerase
activity in bacteria. The RNA polymerase enzymes in bacteria are structurally di erent from
those in eukaryotes, providing for selective toxicity against bacterial cells. It is used for the
treatment of a variety of infections, but its primary use, often in a cocktail with other
antibacterial drugs, is against mycobacteria that cause tuberculosis. Despite the selectivity
of its mechanism, rifampin can induce liver enzymes to increase metabolism of other drugs
being administered (antagonism), leading to hepatotoxicity (liver toxicity) and negatively
in uencing the bioavailability and therapeutic e ect of the companion drugs.
One member of the quinolone family, a group of synthetic antimicrobials, is nalidixic acid. It
was discovered in 1962 as a byproduct during the synthesis of chloroquine, an antimalarial
drug. Nalidixic acid selectively inhibits the activity of bacterial DNA gyrase, blocking DNA
replication. Chemical modi cations to the original quinolone backbone have resulted in the
production of uoroquinolones, like cipro oxacin and levo oxacin, which also inhibit the
activity of DNA gyrase. Cipro oxacin and levo oxacin are e ective against a broad spectrum
of gram-positive or gram-negative bacteria, and are among the most commonly prescribed
antibiotics used to treat a wide range of infections, including urinary tract infections,
respiratory infections, abdominal infections, and skin infections. However, despite their
selective toxicity against DNA gyrase, side e ects associated with di erent uoroquinolones
include phototoxicity, neurotoxicity, cardiotoxicity, glucose metabolism dysfunction, and
increased risk for tendon rupture.
Table 5. Drugs That Inhibit Bacterial Nucleic Acid Synthesis
Mechanisms of
Action
Drug Class
Speci c
Drugs
Spectrum of
activity
Clinical Use
Inhibits bacterial
RNA
polymerase
activity and
blocks
transcription,
killing the cell
Rifamycin Rifampin
Narrow spectrum
with activity against
gram-positive and
limited numbers of
gram-negative
bacteria. Also
active against
Mycobacterium
tuberculosis.
Combination
therapy for
treatment of
tuberculosis
Inhibits the
activity of DNA
gyrase and
blocks DNA
replication,
killing the cell
Fluoroquinolones
Cipro oxacin,
o oxacin,
moxi oxacin
Broad spectrum
against gram-
positive and gram-
negative bacteria
Wide variety
of skin and
systemic
infections
THINK ABOUT IT
16. Why do inhibitors of bacterial nucleic acid synthesis not target host cells?
Inhibitors of Metabolic Pathways
Some synthetic drugs control bacterial infections by functioning as antimetabolites,
competitive inhibitors for bacterial metabolic enzymes (Table 6). The sulfonamides (sulfa
drugs) are the oldest synthetic antibacterial agents and are structural analogues of para-
aminobenzoic acid (PABA), an early intermediate in folic acid synthesis (Figure 4). By
inhibiting the enzyme involved in the production of dihydrofolic acid, sulfonamides block
bacterial biosynthesis of folic acid and, subsequently, pyrimidines and purines required for
nucleic acid synthesis. This mechanism of action provides bacteriostatic inhibition of growth
against a wide spectrum of gram-positive and gram-negative pathogens. Because humans
obtain folic acid from food instead of synthesizing it intracellularly, sulfonamides are
selectively toxic for bacteria. However, allergic reactions to sulfa drugs are common. The
sulfones are structurally similar to sulfonamides but are not commonly used today except for
the treatment of Hansen’s disease (leprosy).
Table 6. Antimetabolite Drugs
Metabolic
Pathway
Target
Mechanism of Action Drug Class Speci c Drugs
Spectrum of
Activity
Folic acid
synthesis
Inhibits the enzyme
involved in production
of dihydrofolic acid
Sulfonamides Sulfamethoxazole
Broad
spectrum
against gram-
positive and
gram-negative
bacteria
Sulfones Dapsone
Inhibits the enzyme
involved in the
production of
tetrahydrofolic acid
Not
applicable
Trimethoprim
Broad
spectrum
against gram-
positive and
gram-negative
bacteria
Mycolic
acid
synthesis
Interferes with the
synthesis of mycolic
acid
Not
applicable
Isoniazid
Narrow
spectrum
against
Mycobacterium
spp., including
M. tuberculosis
Trimethoprim is a synthetic antimicrobial compound that serves as an antimetabolite within
the same folic acid synthesis pathway as sulfonamides. However, trimethoprim is a
structural analogue of dihydrofolic acid and inhibits a later step in the metabolic pathway
(Figure 4). Trimethoprim is used in combination with the sulfa drug sulfamethoxazole to treat
17. urinary tract infections, ear infections, and bronchitis. As discussed, the combination of
trimethoprim and sulfamethoxazole is an example of antibacterial synergy. When used alone,
each antimetabolite only decreases production of folic acid to a level where bacteriostatic
inhibition of growth occurs. However, when used in combination, inhibition of both steps in
the metabolic pathway decreases folic acid synthesis to a level that is lethal to the bacterial
cell. Because of the importance of folic acid during fetal development, sulfa drugs and
trimethoprim use should be carefully considered during early pregnancy.
The drug isoniazid is an antimetabolite with speci c toxicity for mycobacteria and has long
been used in combination with rifampin or streptomycin in the treatment of tuberculosis. It
is administered as a prodrug, requiring activation through the action of an intracellular
bacterial peroxidase enzyme, forming isoniazid-nicotinamide adenine dinucleotide (NAD)
and isoniazid-nicotinamide adenine dinucleotide phosphate (NADP), ultimately preventing
the synthesis of mycolic acid, which is essential for mycobacterial cell walls. Possible side
e ects of isoniazid use include hepatotoxicity, neurotoxicity, and hematologic toxicity
(anemia).
Figure 4. Click for a larger image. Sulfonamides and trimethoprim are examples of
antimetabolites that interfere in the bacterial synthesis of folic acid by blocking purine and
pyrimidine biosynthesis, thus inhibiting bacterial growth.
18. THINK ABOUT IT
How do sulfonamides and trimethoprim selectively target bacteria?
Inhibitor of ATP Synthase
Bedaquiline, representing the synthetic antibacterial class of compounds called the
diarylquinolones, uses a novel mode of action that speci cally inhibits mycobacterial
growth. Although the speci c mechanism has yet to be elucidated, this compound appears
to interfere with the function of ATP synthases, perhaps by interfering with the use of the
hydrogen ion gradient for ATP synthesis by oxidative phosphorylation, leading to reduced
ATP production. Due to its side e ects, including hepatotoxicity and potentially lethal heart
arrhythmia, its use is reserved for serious, otherwise untreatable cases of tuberculosis.
To learn more about the general principles of antimicrobial therapy and bacterial modes of
action, visit Michigan State University’s Antimicrobial Resistance Learning Site, particularly
pages 6 through 9.
CLINICAL FOCUS: NAKRY, PART 2
This example continues Nakry’s story that started in History of Chemotherapy and
Chemotherapy
Antimicrobial Discovery.
Reading thorough Nakry’s health history, the doctor noticed that during her
hospitalization in Vietnam, she was catheterized and received the antimicrobial
drugs ceftazidime and metronidazole. Upon learning this, the doctor ordered a
CT scan of Nakry’s abdomen to rule out appendicitis; the doctor also requested
blood work to see if she had an elevated white blood cell count, and ordered a
urine analysis test and urine culture to look for the presence of white blood cells,
red blood cells, and bacteria.
Nakry’s urine sample came back positive for the presence of bacteria, indicating a
urinary tract infection (UTI). The doctor prescribed cipro oxacin. In the meantime,
her urine was cultured to grow the bacterium for further testing.
What types of antimicrobials are typically prescribed for UTIs?
Based upon the antimicrobial drugs she was given in Vietnam, which of the
antimicrobials for treatment of a UTI would you predict to be ine ective?
19. We’ll return to Nakry’s example in later pages.
KEY CONCEPTS AND SUMMARY
Antibacterial compounds exhibit selective toxicity, largely due to
di erences between prokaryotic and eukaryotic cell structure.
Cell wall synthesis inhibitors, including the β-lactams, the glycopeptides,
and bacitracin, interfere with peptidoglycan synthesis, making bacterial
cells more prone to osmotic lysis.
There are a variety of broad-spectrum, bacterial protein synthesis inhibitors
that selectively target the prokaryotic 70S ribosome, including those that
bind to the 30S subunit (aminoglycosides and tetracyclines) and others
that bind to the 50S subunit (macrolides, lincosamides, chloramphenicol,
and oxazolidinones).
Polymyxins are lipophilic polypeptide antibiotics that target the
lipopolysaccharide component of gram-negative bacteria and ultimately
disrupt the integrity of the outer and inner membranes of these bacteria.
The nucleic acid synthesis inhibitors rifamycins and uoroquinolones target
bacterial RNA transcription and DNA replication, respectively.
Some antibacterial drugs are antimetabolites, acting as competitive
inhibitors for bacterial metabolic enzymes. Sulfonamides and trimethoprim
are antimetabolites that interfere with bacterial folic acid synthesis.
Isoniazid is an antimetabolite that interferes with mycolic acid synthesis in
mycobacteria.
MULTIPLE CHOICE
Which of the following terms refers to the ability of an antimicrobial drug to harm
the target microbe without harming the host?
a. mode of action
b. therapeutic level
c. spectrum of activity
d. selective toxicity
20. Show Answer
Which of the following is not a type of β-lactam antimicrobial?
a. penicillins
b. glycopeptides
c. cephalosporins
d. monobactams
Show Answer
Which of the following does not bind to the 50S ribosomal subunit?
a. tetracyclines
b. lincosamides
c. macrolides
d. chloramphenicol
Show Answer
Which of the following antimicrobials inhibits the activity of DNA gyrase?
a. polymyxin B
b. clindamycin
c. nalidixic acid
d. rifampin
Show Answer
FILL IN THE BLANK
Selective toxicity antimicrobials are easier to develop against bacteria because
they are ________ cells, whereas human cells are eukaryotic.
Show Answer
TRUE/FALSE
β-lactamases can degrade vancomycin.
21. Previous Next
Show Answer
THINK ABOUT IT
. If human cells and bacterial cells perform transcription, how are the
rifamycins speci c for bacterial infections?
. What bacterial structural target would make an antibacterial drug selective
for gram-negative bacteria? Provide one example of an antimicrobial
compound that targets this structure.
. In considering the cell structure of prokaryotes compared with that of
eukaryotes, propose one possible reason for side e ects in humans due to
treatment of bacterial infections with protein synthesis inhibitors.