This document summarizes a lecture on inhibitors of cell wall synthesis and protein biosynthesis. It discusses various classes of antibiotics, including carbapenems, monobactams, beta-lactamase inhibitors, peptide antibiotics (polymyxins, glycopeptides, bacitracin), and protein synthesis inhibitors. It provides details on specific antibiotics, their mechanisms of action, spectra of activity, pharmacokinetics, toxicities, and clinical uses. The lecture was presented by Dr. G. Kattam Maiyoh.
To understand the mechanisms of antimicrobial action and the classification of antimicrobial drugs.
To explain the process of microbial resistance.
To understand the spread of resistant microbes.
Outlines the prevention of microbial resistance.
The most common mode of action for antibiotics is the inhibition of cell wall synthesis. Antibiotics that inhibit cell wall synthesis work because of the fact that most eubacteria have peptidoglycan-based cell walls but mammals do not. Growth is prevented by inhibiting peptidoglycan synthesis. Thus these antibiotics only work for actively growing bacteria. The cell wall of new bacteria that grew in the presence of cell-wall-synthesis inhibitors is deprived of peptidoglycan. These bacteria will be subjected to osmotic lysis.In addition, gram-negative bacteria generally are less susceptible to inhibitors of cell wall synthesis than are gram-positive bacteria. In the former cell wall synthesis inhibitors fail to reach the cell wall because they are blocked by the gram-negative outer membrane.Penicillin is the classic example of an inhibitor of cell wall synthesis. Other examples include: ampicillin, bacitracin, carbapenems, cephalosporin, methicillin, oxacillin and vancomycin
To understand the mechanisms of antimicrobial action and the classification of antimicrobial drugs.
To explain the process of microbial resistance.
To understand the spread of resistant microbes.
Outlines the prevention of microbial resistance.
The most common mode of action for antibiotics is the inhibition of cell wall synthesis. Antibiotics that inhibit cell wall synthesis work because of the fact that most eubacteria have peptidoglycan-based cell walls but mammals do not. Growth is prevented by inhibiting peptidoglycan synthesis. Thus these antibiotics only work for actively growing bacteria. The cell wall of new bacteria that grew in the presence of cell-wall-synthesis inhibitors is deprived of peptidoglycan. These bacteria will be subjected to osmotic lysis.In addition, gram-negative bacteria generally are less susceptible to inhibitors of cell wall synthesis than are gram-positive bacteria. In the former cell wall synthesis inhibitors fail to reach the cell wall because they are blocked by the gram-negative outer membrane.Penicillin is the classic example of an inhibitor of cell wall synthesis. Other examples include: ampicillin, bacitracin, carbapenems, cephalosporin, methicillin, oxacillin and vancomycin
Penicillin is one of the foremost important antibiotic in the world. It is used against the gram positive bacteria. But the resistance mechanism has been developed by them. But researchers are taking step to synthesis such synthetic penicillin for multipurpose use.
Microbiology is the study of microorganisms.
The overall theme of the Microbiology course is to study the relationship between microbes and our lives.
Microorganisms (microbes) are organisms that are too small to be seen with the unaided eye, and usually require a microscope to be seen.
This relationship involves harmful effects such as diseases and food spoilage as well as many beneficial effects.
Hello friends. In this PPT I am talking about anti-fungal drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
Penicillin is one of the foremost important antibiotic in the world. It is used against the gram positive bacteria. But the resistance mechanism has been developed by them. But researchers are taking step to synthesis such synthetic penicillin for multipurpose use.
Microbiology is the study of microorganisms.
The overall theme of the Microbiology course is to study the relationship between microbes and our lives.
Microorganisms (microbes) are organisms that are too small to be seen with the unaided eye, and usually require a microscope to be seen.
This relationship involves harmful effects such as diseases and food spoilage as well as many beneficial effects.
Hello friends. In this PPT I am talking about anti-fungal drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
Antibiotics,antibiotics resistances,classification of antibiotics,misuse of antibiotics details discussed here. for more information visit my blog helpful for pharmacy and medical student.thanks.
http://mydreamlan.wordpress.com/category/education/
Exploration of a potential FtsZ inhibitors as new scaffolds by Ligand and Str...Pavan Kumar
Multi-drug resistant Mtb is a major worldwide health problem. Therefore, it is need to develop new antibiotics with novel modes of action to overcome this emerging resistance problem.
FtsZ (Filamentous temperature-sensitive protein Z ) Drug Target for Tuberculosis
FtsZ is the key protein of bacterial cell division, filament-forming GTPase and a structural homologue of eukaryotic tubulin.
It interacts with membrane-associated proteins FtsA and ZipA and assembles into a ring like structure at the midcell, this ring is known as Z-ring.
The formation of the Z-ring is facilitated by the ability of FtsZ to bind to GTP, which enables polymerization of FtsZ, resulting in the creation of straight protofilaments.
It is the first protein to move to the division site, and is essential for recruiting other proteins that produce a new cell wall between the dividing cells. So it is an emergent target for new antibiotics.
Mechanism of action of major antibiotic classes including betal lactam agents, aminoglycosides, macrolides, tetracyclines, quinolons, vancomycin, oxazolidionons. Detailed review and illustrations
biosynthesis of the cell wall and antibioticsSafaFallah
the cell wall description and the difference between the gram positive and negative bacteria and the structure of peptidoglycan and the biosynthesis of the cell wall (peptidoglycan) in bacteria and the end is with some groups of antibiotics that inhibit the synthesis of peptidoglycan in different ways and targets the bacteria.
About Glutathione synthesis, Functions of Glutathione, and Pharmacology of Glutathione. Glutathione is distributed in high concentrations in aerobics organisms, for this reason, constitutes one of the mechanisms of antioxidant defense essential for the cell.
1. Bio 319: Antibiotics
Lecture Three
Topic: Inhibitors of cell wall synthesis (brief)
Inhibitors of protein biosynthesis
Lecturer: Dr. G. Kattam Maiyoh
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2. Inhibitors of Cell Wall Synthesis
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3. Carbapenems
• Beta-lactam ring is
fused to a 5 member
ring system
• Effect on microbes
and pharmacology
of carbapenems
similar to penicillins
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4. Selected Carbapenems
• Imipenem
– Broad spectrum including anaerobes
and Pseudomonas aeruginosa
– Parentally administered
– Must be combined with cilastatin to be
absorbed
– Excreted by kidneys
• Meropenem, ertapenem, and doripenem
are similar to imipenem but don’t need co-
administration with cilastatin
cilastatin chemical compound which inhibits the human enzyme dehydropeptidase
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5. Toxicity/Contraindications
of Carbapenems
• Nausea and vomiting (common)
• Hypersensitivity reactions (uncommon)
– Essentially the same as for penicillins, exception
is the monobactam
– Cross-reactivity is possible, exception is the
monobactam
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6. Aztrenam – a monobactam
• Works only on Gm -ve, including Pseudomonas
aeruginosa
• Useful for treating G-ve infections that require
a beta-lactam because it does not elicit
hypersensitivity reactions
• Monobactam - beta-lactam compounds
wherein the beta-lactam ring is alone and not
fused to another ring
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7. Beta-lactamase inhibitors
a. Clavulanic acid
– Irreversible inhibitor of β-lactamase
– Good oral absorption
– Combined with amoxicillin or ticarcillin
b. Sulbactam
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8. Peptide Antibiotics
Peptide Antibiotics are drugs with
polypeptides structure
Sub-group of Peptide Antibiotics
Polymyxins
Glycopeptides
Bacitracin
Streptogramins
Each drug group has its own
mechanism of action
4 groups and 4 mechanism
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9. • Peptide antibiotics – May be
further classified as follows;
–Polymyxins
»Polymyxin B
»Colistin
–Glycopeptides
»Vancomycin
»Teicoplanin
»Avoparcin
–Bacitracin
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10. Polymyxins
Drug members
Polymyxin B
Colistin (Polymyxin E)
Mechanism of action
Detergent-like action
Damage to cell membrane function
Bind to LPS and destroy outer membrane
of Gram-negative bacteria
Bactericidal
Concentration-dependent
Non-selective on bacterial membrane
Spectrum of activity
Gram-negative bacteria
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11. Polymyxins
• Pharmacokinetics
– Not absorbed via GI tract
– If injection, drug accumulated and slowly
excreted
• Toxicities
– Highly toxic if systemic injection
– Nephrotoxic
– Neurotoxic
• Clinical uses
– Oral treatment
– Local treatment
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12. Glycopeptides
• Group members
– Vancomycin
• Antibacterial activity
– Inhibition of cell wall synthesis
– Active against Gram-positive bacteria
• Not absorbed orally, must administered IV
• High toxicity
– Local irritation , ototoxicity, nephrotoxicity
• Clinical uses
– Hardly used in animals
– Used only resistant case i.e. to beta-lactams
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13. Bacitracin
• Only member is Bacitracin
• Drug activity
– Inhibit cell wall synthesis
– Activity on Gram-positive bacteria
– Bactericidal
• Nephrotoxic if systemic injection
• Clinical uses – the same as polymyxin
– Oral – as growth promoter
– Local or topical drugs
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14. Antibiotics that Inhibit Protein Synthesis
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16. Inhibition of Protein Synthesis by Antibiotics
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03/Sem02/2013 Figure 20.4
17. Review of Initiation of Protein Synthesis
1 3
30S 2 GTP
1 2 3 GTP
Initiation Factors
f-met-tRNA
mRNA
Spectinomycin
3
GDP + Pi
50S
2
P A
1 1
2 GTP
70S Aminoglycosides
30S
Initiation Initiation
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Complex
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18. Review of Elongation of Protein Synthesis
P A Tetracycline P A
Tu GTP Tu GDP + Pi
GTP Ts
Ts Tu
Ts GDP
Chloramphenicol
GDP
Fusidic Acid +
GTP
G
G GDP + Pi
G GTP
P A P A
Erythromycin
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20. Protein Synthesis Inhibitors
• Mostly bacteriostatic
• Selectivity due to differences in prokaryotic
and eukaryotic ribosomes
• Some toxicity - eukaryotic 70S ribosomes
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21. Antimicrobials that Bind to the 30S
Ribosomal Subunit
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22. a) Aminoglycosides (bactericidal)
streptomycin, kanamycin, gentamicin, tobramycin, amikacin,
netilmicin, neomycin (topical)
• Mode of action - The aminoglycosides irreversibly bind
to the 16S ribosomal RNA and freeze the 30S initiation
complex (30S-mRNA-tRNA) so that no further initiation
can occur.
• They also slow down protein synthesis that has already
initiated and induce misreading of the mRNA.
– By binding to the 16 S r-RNA the aminoglycosides increase
the affinity of the A site for t-RNA regardless of the anticodon
specificity.
• May also destabilize bacterial membranes.
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23. Microbe Library
American Society for Microbiology
www.microbelibrary.org
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24. b) Aminoglycosides (bactericidal)
streptomycin, kanamycin, gentamicin, tobramycin, amikacin,
netilmicin, neomycin (topical)
• Spectrum of Activity –Effective against many gram-
negative and some gram-positive bacteria;
• Not useful for anaerobic (oxygen required for uptake of
antibiotic) or intracellular bacteria.
• Resistance - Common
• Synergy - The aminoglycosides synergize with β -lactam
antibiotics. The β -lactams inhibit cell wall synthesis and
thereby increase the permeability of the aminoglycosides.
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25. c) Tetracyclines (bacteriostatic)
tetracycline, minocycline and doxycycline
• Mode of action - The tetracyclines reversibly bind to the 30S
ribosome and inhibit binding of aminoacyl-t-RNA to the acceptor site
on the 70S ribosome.
• Spectrum of activity - Broad spectrum; Useful against intracellular
bacteria
• Resistance - Common
• Adverse effects - Destruction of normal intestinal flora resulting in
increased secondary infections; staining and impairment of the
structure of bone and teeth.
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26. d) Spectinomycin (bacteriostatic)
• Mode of action - Spectinomycin reversibly interferes with m-RNA
interaction with the 30S ribosome. It is structurally similar to the
aminoglycosides but does not cause misreading of mRNA.
• Spectrum of activity - Used in the treatment of penicillin-resistant
Neisseria gonorrhoeae
• Resistance - Rare in Neisseria gonorrhoeae
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27. Antimicrobials that Bind to the 50S
Ribosomal Subunit
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28. a) Chloramphenicol, Lincomycin,
Clindamycin (bacteriostatic)
• Mode of action - These antimicrobials bind to the 50S ribosome and
inhibit peptidyl transferase activity.
• Spectrum of activity - Chloramphenicol - Broad range;
Lincomycin and clindamycin - Restricted range
• Resistance - Common
• Adverse effects - Chloramphenicol is toxic (bone marrow suppression) but
is used in the treatment of bacterial meningitis.
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29. b) Macrolides (bacteriostatic)
erythromycin, clarithromycin, azithromycin, spiramycin
• Mode of action - The macrolides inhibit translocation.
• Spectrum of activity - Gram-positive bacteria,
Mycoplasma, Legionella
• Resistance - Common
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30. Macrolides : Classification
• Macrolides are drugs with lactone ring
structure
• Sub-groups are based on no. of ring atom
– 12-membered ring macrolides
– 13-membered
– 14-membered (many drugs)
– 15-membered
– 16-membered (many drugs)
• Special groups
– Azalides – name for 15-membered
– Triamilides – name for tulathromycin
(combination of 13- and 15-membered)
– Ketolides – name for 14-membered with 3
keto group
32. Macrolides – general
properties
• Mechanism of
action
– Inhibit protein
synthesis
– Bind to 50S
ribosomal unit
– Bacteriostatic
• Spectrum of
activity
– Gram-positive
– Some Gram-
negative
34. Macrolides
Additional properties
of Macrolides
• Anti-inflammatory
effect
– Inhibitory effect on
neutrophils
– inhibit
proinflammatory
cytokines
– Useful for treatment
of inflammatory
35. Erythromycin
• Erythromycin is a standard or basic drug of
macrolides
• Other drug members are usually compared
with erythromycin
• Important adverse effect - severe diarrhea
– Especially in adult horse and ruminants
• Clinical uses
– Second choice (alternative drug)
– Small animals
– Fowls
– Some cases in ruminants
– Not used in pigs
36. Tylosin and Spiramycin
• Tylosin and Spiramycin
– Activities are similar
to erythromycin
– Good activity on
Mycoplasma
• Clinical uses
– Macrolides used in
ruminants and pigs
– Used for Mycoplasma
infection
37. Advanced generation
Macrolides
Example drugs
Roxithromycin
Dirithromycin
Clarithromycin
Azithromycin
General activity – the same as erythromycin
Better Pharmacokinetic properties
Acid stable
Fewer GI side effect
Higher oral availability
Longer serum half-lives
Higher tissue concentrations
38. Ketolides
• Ketolides are 14-
membered ring
macrolides with 3
keto group
• Specific drugs
– Telithromycin
– Cethromycin (still
in clinical study)
• Important
properties
– Less resistance
– Good activities on
39. Antimicrobials that Interfere with
Elongation Factors
Selectivity due to differences in prokaryotic and eukaryotic
elongation factors
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40. Fusidic acid (bacteriostatic)
• Mode of action - Fusidic acid binds to elongation factor G (EF-G) and
inhibits release of EF-G from the EF-G/GDP complex.
• Spectrum of activity - Gram-positive cocci
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