1. The document discusses various antibiotics and their mechanisms of action on bacterial cells, focusing on how they inhibit important metabolic processes.
2. Key antibiotic classes are described that inhibit cell wall synthesis, protein synthesis, DNA replication, and folic acid biosynthesis. Examples like penicillins, aminoglycosides, fluoroquinolones, and sulfonamides are provided.
3. The major sites of antibiotic action discussed are the bacterial cell wall, cytoplasmic membrane, DNA, ribosomes, and metabolic pathways. How each antibiotic class interferes with these sites is explained.
Signal transduction in plant defence responsesrkravikirankt
Plant respond to the attack of diseases by triggering various bio-molecules insider their system to combat the infection and establishment of the pathogens. these response operate in specified pathways mediated by many enzymes starting from the infection site to the nucleus which together constitute the signal transduction pathway.
This ppts is based upon the recent adavancement and methodology about mitochondrial transformation. What is organellar transformation and what is the importance in contemporary time.
In this presentation I have mentioned whatever the possible relevant content required for the aptamer based drug delivery.
Citation Is done at the end of slide.
Content is up to date & true to my belief.
Thanks & Best Regards.
Anurag Pandey
B.Pharm (FACULTY OF PHARMACY, INVERTIS UNIVERSITY)
M.Pharm (INSTITUTE OF PHARMACY, NIRMA UNIVERSITY)
Email :- anurag.dmk05@gmail.com
Signal transduction in plant defense responsesVINOD BARPA
Signal transduction a Process by which a cell converts one kind of signal into another. Plant disease resistance and susceptibility are gov¬erned by the combined genotypes of host and pathogen and depend on a complex exchange of signals and responses occurring under given environmental con¬ditions. During the long process of host-pathogen co-evolution, plants have developed various elaborate mechanisms to ward off pathogen attack. Whereas some of these defense mechanisms are preformed and provide physical and chemical barriers to hinder pathogen infection, others are induced only after pa¬thogen attack. Similar to animal immune responses, induced plant defense responses involve a network of signal transduction and the rapid activation of gene expression following pathogen infection. They do not have immune system and locomotary organs to escape environmental challenges and biotic stresses. In plant, nature has provided them some preformed and inducible defense resistance. Host recognition of invading pathogen is often determined by the so called “gene for gene” interaction between avirulence (avr) gene of pathogen and corresponding resistance (R) gene of host (Flor, 1971) which encode receptor for the recognition of specific elicitor or ligand encoded directly or indirectly by pathogen avr gene. Recent studies have revealed intriguing parallels between animal and plant defense responses as demonstrated by the structural and functional conservation of some of their signal transduction processes. Furthermore, signaling components such as G proteins, NADPH oxidase, H202, salicylic acid (SA, and aspirin), mitogen-activated protein kinases (MAPK), and transcription factors have been shown to be associated with or participate in both animal and plant defense responses, suggesting the presence of con¬served signaling pathways for host defenses in diverse higher eukaryotes.
Penicillin binding proteins are a group of proteins found in different organisms that have high
affinity for penicillin and bind themselves to penicillin. These proteins are made up of many
types of bacteria. They bind themselves in different ways and as such there are both cytoplasmic
bound penicillin binding proteins and membrane bound ones.
This is lecturer notes on pharmacology & toxicology for B.V.Sc & A.H. Seventh semester students.This may useful for other institute veterinary students.Please send your comment and suggestion;jibachhashah@gmail.com,mob.9845024121
This slide have the information about chemotherapy:- the treatment of disease by means of chemicals that have a specific toxic effect upon the disease-producing microorganisms or that selectively destroy cancerous tissue.Also include the drug resistance:-Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial.
Signal transduction in plant defence responsesrkravikirankt
Plant respond to the attack of diseases by triggering various bio-molecules insider their system to combat the infection and establishment of the pathogens. these response operate in specified pathways mediated by many enzymes starting from the infection site to the nucleus which together constitute the signal transduction pathway.
This ppts is based upon the recent adavancement and methodology about mitochondrial transformation. What is organellar transformation and what is the importance in contemporary time.
In this presentation I have mentioned whatever the possible relevant content required for the aptamer based drug delivery.
Citation Is done at the end of slide.
Content is up to date & true to my belief.
Thanks & Best Regards.
Anurag Pandey
B.Pharm (FACULTY OF PHARMACY, INVERTIS UNIVERSITY)
M.Pharm (INSTITUTE OF PHARMACY, NIRMA UNIVERSITY)
Email :- anurag.dmk05@gmail.com
Signal transduction in plant defense responsesVINOD BARPA
Signal transduction a Process by which a cell converts one kind of signal into another. Plant disease resistance and susceptibility are gov¬erned by the combined genotypes of host and pathogen and depend on a complex exchange of signals and responses occurring under given environmental con¬ditions. During the long process of host-pathogen co-evolution, plants have developed various elaborate mechanisms to ward off pathogen attack. Whereas some of these defense mechanisms are preformed and provide physical and chemical barriers to hinder pathogen infection, others are induced only after pa¬thogen attack. Similar to animal immune responses, induced plant defense responses involve a network of signal transduction and the rapid activation of gene expression following pathogen infection. They do not have immune system and locomotary organs to escape environmental challenges and biotic stresses. In plant, nature has provided them some preformed and inducible defense resistance. Host recognition of invading pathogen is often determined by the so called “gene for gene” interaction between avirulence (avr) gene of pathogen and corresponding resistance (R) gene of host (Flor, 1971) which encode receptor for the recognition of specific elicitor or ligand encoded directly or indirectly by pathogen avr gene. Recent studies have revealed intriguing parallels between animal and plant defense responses as demonstrated by the structural and functional conservation of some of their signal transduction processes. Furthermore, signaling components such as G proteins, NADPH oxidase, H202, salicylic acid (SA, and aspirin), mitogen-activated protein kinases (MAPK), and transcription factors have been shown to be associated with or participate in both animal and plant defense responses, suggesting the presence of con¬served signaling pathways for host defenses in diverse higher eukaryotes.
Penicillin binding proteins are a group of proteins found in different organisms that have high
affinity for penicillin and bind themselves to penicillin. These proteins are made up of many
types of bacteria. They bind themselves in different ways and as such there are both cytoplasmic
bound penicillin binding proteins and membrane bound ones.
This is lecturer notes on pharmacology & toxicology for B.V.Sc & A.H. Seventh semester students.This may useful for other institute veterinary students.Please send your comment and suggestion;jibachhashah@gmail.com,mob.9845024121
This slide have the information about chemotherapy:- the treatment of disease by means of chemicals that have a specific toxic effect upon the disease-producing microorganisms or that selectively destroy cancerous tissue.Also include the drug resistance:-Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial.
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.
Observability Concepts EVERY Developer Should Know -- DeveloperWeek Europe.pdfPaige Cruz
Monitoring and observability aren’t traditionally found in software curriculums and many of us cobble this knowledge together from whatever vendor or ecosystem we were first introduced to and whatever is a part of your current company’s observability stack.
While the dev and ops silo continues to crumble….many organizations still relegate monitoring & observability as the purview of ops, infra and SRE teams. This is a mistake - achieving a highly observable system requires collaboration up and down the stack.
I, a former op, would like to extend an invitation to all application developers to join the observability party will share these foundational concepts to build on:
State of ICS and IoT Cyber Threat Landscape Report 2024 previewPrayukth K V
The IoT and OT threat landscape report has been prepared by the Threat Research Team at Sectrio using data from Sectrio, cyber threat intelligence farming facilities spread across over 85 cities around the world. In addition, Sectrio also runs AI-based advanced threat and payload engagement facilities that serve as sinks to attract and engage sophisticated threat actors, and newer malware including new variants and latent threats that are at an earlier stage of development.
The latest edition of the OT/ICS and IoT security Threat Landscape Report 2024 also covers:
State of global ICS asset and network exposure
Sectoral targets and attacks as well as the cost of ransom
Global APT activity, AI usage, actor and tactic profiles, and implications
Rise in volumes of AI-powered cyberattacks
Major cyber events in 2024
Malware and malicious payload trends
Cyberattack types and targets
Vulnerability exploit attempts on CVEs
Attacks on counties – USA
Expansion of bot farms – how, where, and why
In-depth analysis of the cyber threat landscape across North America, South America, Europe, APAC, and the Middle East
Why are attacks on smart factories rising?
Cyber risk predictions
Axis of attacks – Europe
Systemic attacks in the Middle East
Download the full report from here:
https://sectrio.com/resources/ot-threat-landscape-reports/sectrio-releases-ot-ics-and-iot-security-threat-landscape-report-2024/
Dev Dives: Train smarter, not harder – active learning and UiPath LLMs for do...UiPathCommunity
💥 Speed, accuracy, and scaling – discover the superpowers of GenAI in action with UiPath Document Understanding and Communications Mining™:
See how to accelerate model training and optimize model performance with active learning
Learn about the latest enhancements to out-of-the-box document processing – with little to no training required
Get an exclusive demo of the new family of UiPath LLMs – GenAI models specialized for processing different types of documents and messages
This is a hands-on session specifically designed for automation developers and AI enthusiasts seeking to enhance their knowledge in leveraging the latest intelligent document processing capabilities offered by UiPath.
Speakers:
👨🏫 Andras Palfi, Senior Product Manager, UiPath
👩🏫 Lenka Dulovicova, Product Program Manager, UiPath
The Metaverse and AI: how can decision-makers harness the Metaverse for their...Jen Stirrup
The Metaverse is popularized in science fiction, and now it is becoming closer to being a part of our daily lives through the use of social media and shopping companies. How can businesses survive in a world where Artificial Intelligence is becoming the present as well as the future of technology, and how does the Metaverse fit into business strategy when futurist ideas are developing into reality at accelerated rates? How do we do this when our data isn't up to scratch? How can we move towards success with our data so we are set up for the Metaverse when it arrives?
How can you help your company evolve, adapt, and succeed using Artificial Intelligence and the Metaverse to stay ahead of the competition? What are the potential issues, complications, and benefits that these technologies could bring to us and our organizations? In this session, Jen Stirrup will explain how to start thinking about these technologies as an organisation.
Pushing the limits of ePRTC: 100ns holdover for 100 daysAdtran
At WSTS 2024, Alon Stern explored the topic of parametric holdover and explained how recent research findings can be implemented in real-world PNT networks to achieve 100 nanoseconds of accuracy for up to 100 days.
Elevating Tactical DDD Patterns Through Object CalisthenicsDorra BARTAGUIZ
After immersing yourself in the blue book and its red counterpart, attending DDD-focused conferences, and applying tactical patterns, you're left with a crucial question: How do I ensure my design is effective? Tactical patterns within Domain-Driven Design (DDD) serve as guiding principles for creating clear and manageable domain models. However, achieving success with these patterns requires additional guidance. Interestingly, we've observed that a set of constraints initially designed for training purposes remarkably aligns with effective pattern implementation, offering a more ‘mechanical’ approach. Let's explore together how Object Calisthenics can elevate the design of your tactical DDD patterns, offering concrete help for those venturing into DDD for the first time!
Transcript: Selling digital books in 2024: Insights from industry leaders - T...BookNet Canada
The publishing industry has been selling digital audiobooks and ebooks for over a decade and has found its groove. What’s changed? What has stayed the same? Where do we go from here? Join a group of leading sales peers from across the industry for a conversation about the lessons learned since the popularization of digital books, best practices, digital book supply chain management, and more.
Link to video recording: https://bnctechforum.ca/sessions/selling-digital-books-in-2024-insights-from-industry-leaders/
Presented by BookNet Canada on May 28, 2024, with support from the Department of Canadian Heritage.
Removing Uninteresting Bytes in Software FuzzingAftab Hussain
Imagine a world where software fuzzing, the process of mutating bytes in test seeds to uncover hidden and erroneous program behaviors, becomes faster and more effective. A lot depends on the initial seeds, which can significantly dictate the trajectory of a fuzzing campaign, particularly in terms of how long it takes to uncover interesting behaviour in your code. We introduce DIAR, a technique designed to speedup fuzzing campaigns by pinpointing and eliminating those uninteresting bytes in the seeds. Picture this: instead of wasting valuable resources on meaningless mutations in large, bloated seeds, DIAR removes the unnecessary bytes, streamlining the entire process.
In this work, we equipped AFL, a popular fuzzer, with DIAR and examined two critical Linux libraries -- Libxml's xmllint, a tool for parsing xml documents, and Binutil's readelf, an essential debugging and security analysis command-line tool used to display detailed information about ELF (Executable and Linkable Format). Our preliminary results show that AFL+DIAR does not only discover new paths more quickly but also achieves higher coverage overall. This work thus showcases how starting with lean and optimized seeds can lead to faster, more comprehensive fuzzing campaigns -- and DIAR helps you find such seeds.
- These are slides of the talk given at IEEE International Conference on Software Testing Verification and Validation Workshop, ICSTW 2022.
Alt. GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using ...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
GraphRAG is All You need? LLM & Knowledge GraphGuy Korland
Guy Korland, CEO and Co-founder of FalkorDB, will review two articles on the integration of language models with knowledge graphs.
1. Unifying Large Language Models and Knowledge Graphs: A Roadmap.
https://arxiv.org/abs/2306.08302
2. Microsoft Research's GraphRAG paper and a review paper on various uses of knowledge graphs:
https://www.microsoft.com/en-us/research/blog/graphrag-unlocking-llm-discovery-on-narrative-private-data/
PHP Frameworks: I want to break free (IPC Berlin 2024)Ralf Eggert
In this presentation, we examine the challenges and limitations of relying too heavily on PHP frameworks in web development. We discuss the history of PHP and its frameworks to understand how this dependence has evolved. The focus will be on providing concrete tips and strategies to reduce reliance on these frameworks, based on real-world examples and practical considerations. The goal is to equip developers with the skills and knowledge to create more flexible and future-proof web applications. We'll explore the importance of maintaining autonomy in a rapidly changing tech landscape and how to make informed decisions in PHP development.
This talk is aimed at encouraging a more independent approach to using PHP frameworks, moving towards a more flexible and future-proof approach to PHP development.
The Art of the Pitch: WordPress Relationships and SalesLaura Byrne
Clients don’t know what they don’t know. What web solutions are right for them? How does WordPress come into the picture? How do you make sure you understand scope and timeline? What do you do if sometime changes?
All these questions and more will be explored as we talk about matching clients’ needs with what your agency offers without pulling teeth or pulling your hair out. Practical tips, and strategies for successful relationship building that leads to closing the deal.
Why You Should Replace Windows 11 with Nitrux Linux 3.5.0 for enhanced perfor...SOFTTECHHUB
The choice of an operating system plays a pivotal role in shaping our computing experience. For decades, Microsoft's Windows has dominated the market, offering a familiar and widely adopted platform for personal and professional use. However, as technological advancements continue to push the boundaries of innovation, alternative operating systems have emerged, challenging the status quo and offering users a fresh perspective on computing.
One such alternative that has garnered significant attention and acclaim is Nitrux Linux 3.5.0, a sleek, powerful, and user-friendly Linux distribution that promises to redefine the way we interact with our devices. With its focus on performance, security, and customization, Nitrux Linux presents a compelling case for those seeking to break free from the constraints of proprietary software and embrace the freedom and flexibility of open-source computing.
Smart TV Buyer Insights Survey 2024 by 91mobiles.pdf91mobiles
91mobiles recently conducted a Smart TV Buyer Insights Survey in which we asked over 3,000 respondents about the TV they own, aspects they look at on a new TV, and their TV buying preferences.
Welcome to the first live UiPath Community Day Dubai! Join us for this unique occasion to meet our local and global UiPath Community and leaders. You will get a full view of the MEA region's automation landscape and the AI Powered automation technology capabilities of UiPath. Also, hosted by our local partners Marc Ellis, you will enjoy a half-day packed with industry insights and automation peers networking.
📕 Curious on our agenda? Wait no more!
10:00 Welcome note - UiPath Community in Dubai
Lovely Sinha, UiPath Community Chapter Leader, UiPath MVPx3, Hyper-automation Consultant, First Abu Dhabi Bank
10:20 A UiPath cross-region MEA overview
Ashraf El Zarka, VP and Managing Director MEA, UiPath
10:35: Customer Success Journey
Deepthi Deepak, Head of Intelligent Automation CoE, First Abu Dhabi Bank
11:15 The UiPath approach to GenAI with our three principles: improve accuracy, supercharge productivity, and automate more
Boris Krumrey, Global VP, Automation Innovation, UiPath
12:15 To discover how Marc Ellis leverages tech-driven solutions in recruitment and managed services.
Brendan Lingam, Director of Sales and Business Development, Marc Ellis
Accelerate your Kubernetes clusters with Varnish CachingThijs Feryn
A presentation about the usage and availability of Varnish on Kubernetes. This talk explores the capabilities of Varnish caching and shows how to use the Varnish Helm chart to deploy it to Kubernetes.
This presentation was delivered at K8SUG Singapore. See https://feryn.eu/presentations/accelerate-your-kubernetes-clusters-with-varnish-caching-k8sug-singapore-28-2024 for more details.
Epistemic Interaction - tuning interfaces to provide information for AI supportAlan Dix
Paper presented at SYNERGY workshop at AVI 2024, Genoa, Italy. 3rd June 2024
https://alandix.com/academic/papers/synergy2024-epistemic/
As machine learning integrates deeper into human-computer interactions, the concept of epistemic interaction emerges, aiming to refine these interactions to enhance system adaptability. This approach encourages minor, intentional adjustments in user behaviour to enrich the data available for system learning. This paper introduces epistemic interaction within the context of human-system communication, illustrating how deliberate interaction design can improve system understanding and adaptation. Through concrete examples, we demonstrate the potential of epistemic interaction to significantly advance human-computer interaction by leveraging intuitive human communication strategies to inform system design and functionality, offering a novel pathway for enriching user-system engagements.
Secstrike : Reverse Engineering & Pwnable tools for CTF.pptx
Microbiology antibiotic
1. Lecture 7- Micro<br />Medical Microbiology<br />Dr. Saleh M.Y.<br /> Tuesday; 13/10/2010<br />Bacteriology<br />Review and Overview<br />Gram +ve cocci:<br />(1) Streptococci, ( St. pyogenes Group A, St. agalactia-B, St. mutnas and St. viridians)<br />(2) Staphylococci (S. aureus, S. epidermidis, S. saprophyticus)<br />(4) Streptococcus pneumonae<br />Gram -ve cocci:<br />(5) Nessireia (N. meningitidis, N. gonorhheae)<br />(6) Sites of infection and names of the Diseases<br />(7) Toxins/mechanisms<br />(8) Pathogenicity <br />(9) Diagnosis (clinical and laboratory diagnosis) <br />(10) Antibiotics/mechnisms/treatment and control<br />BACTERIOLOGY<br />1- Introduction into antibiotics (Dr. Saleh M.Y./one lecture)<br />2- Metabolism-Antibiotic Sensitivity (3-5lectures/ Pharmaceutical Lecturer)<br />Table of Contents<br />Educational Objectives <br />Microbial Metabolism Overview <br />Bacterial Cell Wall Biosynthesis <br />Cytoplasmic Membrane <br />DNA Replication <br />Protein Synthesis <br />Competitive Antagonistic Anitbiotics <br />Summary <br />Educational Objectives<br />In general<br />To explore the relationship between bacterial metabolism and susceptibility to anti-bacterial agents, both physical and chemical <br />To define the mode of action of antibiotics <br />Specific educational objectives (terms and concepts upon which you will be tested) <br />Aminoglycoside antibiotics <br />Antibiotic mode of action <br />b-lactam antibiotics <br />Cell wall inhibitors <br />Competitive antagonistic antibiotics <br />Macrolide antibiotics <br />Protein synthesis inhibitors <br />Quinolone antibiotics <br />Lecture Notes:<br />Microbial Metabolism as Related to Sensitivity to Antibiotics-Overview<br />Many metabolic activities of the bacterial cell differ significantly from those in the human cell. At least theoretically these differences can be exploited in the development of chemotherapeutic agents. Ideally, an antimicrobial agent should have its maximal effect on the bacterial cell and have little or no effect on the human cell. In reality there is almost always some effect on the human be it induction of hypersensitivity or liver or kidney toxicity. Despite some adverse reactions in the human, effective antibiotics have been developed that have one ore more of these modes of action on the bacterial cell: <br />Inhibition of cell wall synthesis <br />Alteration of cell membranes <br />Inhibition of protein synthesis <br />Inhibition of nucleic acid synthesis <br />Antimetabolic activity or competitive antagonism <br />Bacterial Cell Wall Biosynthesis<br />Since bacteria have a cell wall made up of repeating units of peptidoglycan and human cells lack this feature, it would seem that the bacterial cell wall presents an ideal target for chemotherapy. Indeed, this has been the case; the following antibiotics have been developed as inhibitors of cell wall synthesis: <br />A. β-lactam antibiotics <br />1. Penicillins <br /> Penicillin GOxacillinAmpicillin Amoxicillin CloxaciillinPenicillin VNafcillinTicarcillin Carbenicillin DicloxacillinMethicillinPiperacillin<br />2. Cephalosporins First Generation Second Generation Third Generation Fourth Generation <br /> Cefadroxil * Cefaclor *CefdinirCefepime Cefazolin Cefamandole Cefoperaxone Cefelixin * Cefonicid Cefotaxime Cephalothin CeforanideCeftazidime Cephaprin CefotetanCeftibuten Cephradine * Cefoxitin Ceftizoxime CefuroximeCeftriaxone<br /> * Oral Agent <br /> 3. Monobactams <br />4. Thienamycins <br />5. β-lactamase inhibitors (e.g., clavulanic acid)<br />B. Cycloserine, Ethionamide, Isoniazid <br />C. Fosfomycin (Phosphonomycin) <br />D. Vancomycin <br />E. Bacitracin <br />F. Ristocetin <br />G. Fosphomycin (Phosphonomycin) <br />The biosynthesis of peptidoglycan consists of three stages, each of which occurs at a different site in the cell. <br />Stage 1 occurs in the cytoplasm. In this stage the recurring units of the backbone structure of murein, N-acetylglucosamine and N-acetyl-muramylpentapeptide are synthesized in the form of their uracil diphosphate (UDP) derivatives. The only antibiotic that affects this stage of cell wall metabolism is D-cycloserine. D-cycloserine is a structural analog of D-alanine; it binds to the substrate binding site of two enzymes, thus being extremely effective in preventing D-alanine from being incorporated into the N-acetylmuramylpeptide. <br />Structural relationship between cycloserine (left) and D-ala-nine (right).<br />Stage 2 of peptidoglycan synthesis occurs on the inner surface of the cytoplasmic membrane where N-cetylmuramylpeptide is transferred from UDP to a carrier lipid and is then modified to form a complete nascent peptidoglycan subunit. The nature of the modification depends upon the organism. This stage terminates with translocation of the completed subunit to the exterior of the cytoplasmic membrane. The only antibiotic that affects this stage of cell wall synthesis is bacitracin. Bacitracin is an inhibitor of the lipid phosphatase. <br />Bacitracin A. One of a group of polypeptide antibiotics containing a thiazoline ring structure.<br />Stage 3 occurs in the periplasmic space (in gram-negative bacteria) and in the growing peptidoglycan of the cell wall. This is a complex metabolic sequence which offers multiple targets for chemotherapeutic agents. The earliest acting of these are vancomycin and ristocetin. They act by binding to the D-alanyl-D-alanine peptide termini of the nascent peptidoglycan-lipid carrier. This inhibits the enzyme transglycosylase. <br />Stage 3 of biosynthesis continues with transpeptidation and the binding of soluble uncrosslinked, nascent peptidoglycan to the preexisting, crosslinked, insoluble cell wall peptidoglycan matrix. The -lactam antibiotics are structural analogs of the D-alanyl-D-alanine end of the peptidoglycan strand. In the cell wall there are as many as seven enzymes (depending on the bacterial species) which bind peptidoglycan units via their D-alanyl-D-alanine residues. The -lactams fill these substrate binding sites and thus prevent the binding of D-alanyl-D-alanine residues. Enzymes binding -lactam antibiotics are known as penicillin-binding proteins.<br /> <br />The Cytoplasmic Membrane as the Site of Antibiotic Action<br />The cytoplasmic membrane of bacteria is only affected by two clinically-used antibiotics. These are polymyxin B and polymyxin E (colistin). They act by competitively replacing Mg2+ and Ca2+ from negatively charged phosphate groups on membrane lipids. The result is disruption of the membrane. <br /> <br />DNA Replication as the Site of Antimicrobic Action<br />The major group of antibacterial agents that act by blocking DNA synthesis/activity is the quinolone group. <br />Metronidazole represents as an antibiotic active against DNA in a different way. This antibiotic, upon being partially reduced, causes the fragmentation of DNA in an, as yet, undefined way. The antibiotic is only effective against anaerobic bacteria and some parasites. <br />The quinolones all act by blocking the A subunit of DNA gyrase and inducing the formation of a relaxation complex analogue. <br />DNA gyrase introduces negative superhelical turns into duplex DNA, using the energy of ATP. This is the crucial enzyme that maintains the negative superhelical tension of the bacterial chromosome. <br />The sign-inversion mechanism for DNA gyrase.<br />The quinolones include: <br />nalidixic acid - first generation <br />norfloxacin, ciprofloxacin - second generation<br />Protein Synthesis as the Site of Antimicrobic Action<br />Protein synthesis is the end result of two major processes, transcription and translation. An antibiotic that inhibits either of these will inhibit protein synthesis. <br />Transcription <br />During transcription, the genetic information in DNA is transferred to a complementary sequence of RNA nucleotides by the DNA-dependent RNA polymerase. This enzyme is composed of 5 subunits, ß, ß', a, a' and . Antibiotics that either alter the structure of the template DNA or inhibit the RNA polymerase will interfere with the synthesis of RNA, and consequently with protein synthesis. <br />Actinomycin D binds to guanine in DNA, distorting the DNA, and thus blocking transcription. <br />Rifampin (Rifampicin or Rifamycin) inhibits protein synthesis by selective inhibiting the DNA-dependent RNA polymerase. It does this by binding to the ß subunit in a non-covalent fashion. <br />Translation <br />In bacterial cells, the translation of mRNA into protein can be divided into three major phases: initiation, elongation, and termination of the peptide chain. Protein synthesis starts with the association of mRNA, a 30S ribosomal subunit, and formyl-methionyl-transfer RNA (fMet-tRNA) to form a 30S initiation complex. The formation of this complex also requires guanosine triphosphate (GTP) and the participation of three protein initiation factors. The codon AUG is the initiation signal in mRNA and is recognized by the anticodon of fMet-tRNA. A 50S ribosomal subunit is subsequently added to form a 70S initiation complex, and the bound GTP is hydrolyzed. <br />In the elongation phase of protein synthesis, amino acids are added one at a time to a growing polypeptide in a sequence dictated by mRNA. It is this phase that is most susceptible to inhibition by a number of antibiotics. For many of these the ribosome is the target site. There are two binding sites on the ribosome, the P (peptidyl or donor site) and the A (aminoacyl) site. At the end of the initiation stage, the fMet-tRNA molecule is empty. In the first step of the elongation cycle, an aminoacyl-tRNA is inserted into the vacant A site on the ribosome. The particular species inserted depends on the mRNA codon that is positioned in the A site. Protein elongation factors and GTP are required for polypeptide chain elongation. <br />In the next step of the elongation phase, the formylmethionyl residue of the fMet-tRNA located at the peptidyl donor site is released from its linkage to tRNA, and is joined with a peptide bond to the -amino group of the aminoacyl-tRNA in the acceptor site to form a dipeptidyl-tRNA. The enzyme catalyzing this peptide formation is peptidyl transferase, which is part of the 50S ribosomal subunit. <br />Following the formation of a peptide bond, an uncharged tRNA occupies the P site, whereas a dipeptidyl tRNA occupies the A site. The final phase of the elongation cycle is translocation, catalyzed by elongation factor EF-G and requiring GTP. It consists of three movements: <br />(1) the removal of the discharged tRNA from the P site <br />(2) the movement of fMet-aminoacyl-tRNA from the acceptor site to the peptidyl donor site <br />(3) the movement or translocation of the ribosome along the mRNA from the 5' toward the 3' terminus by the length of three nucleotides.<br />After translocation, the stage is prepared for the binding of the next aminoacyl residue to the fMet-aminoacyl-tRNA, each addition requiring aminoacyl-tRNA binding, peptide bond formation, and translocation. Peptidyl-tRNAa replace the fMet-tRNA in the second and in all subsequent cycles. <br />The polypeptide chain grows from the amino terminal toward the carboxyl terminal amino acid and remains linked to tRNA and bound to the mRNA-ribosome complex during elongation of the chain. When completed it is released during chain termination. Termination is triggered when a chain termination signal (UAA, UAG, or UGA) is encountered at the A site of the ribosome. Protein release factors bind to the terminator codons triggering hydrolysis by the peptidyl transferase. The polypeptide is released, and the messenger-ribosome-tRNA complex dissociates. <br />Several medically important antibiotics owe their selective antimicrobial action to a specific attack on the 70S ribosome of bacteria, with mammalian 80S ribosomes left unaffected. Those that act on the 30S ribosome are: <br />Amikacin <br />Gentamycin <br />Kanamycin <br />Neomycin <br />Streptomycin <br />Tobramycin <br />Macrolides: <br /> Azithromycin Dirithromycin Clarithromycin Erythromycin <br /> <br />Antibiotics that act on the 50S portion of the ribosome include: <br />Chloramphenicol <br />Clindamycin <br />Furadantin <br />Fusidic acid <br />Lincomycin <br />Nitrofuran <br />Puromycin <br />Quinopristin/Dalfopristin <br />Spectinomycin <br />Tetracycline <br /> <br /> <br />Lincomycin Clindamycin<br /> <br />Linezolid <br />Puromycin <br /> <br /> <br />Competitive Antagonistic Antibiotics<br />Inhibitors of metabolic pathways via competitive antagonism include: <br /> Isoniazid - Inhibits mycolic acid synthesis <br />Sulfonamides - Inhibit folic acid biosynthesis <br /> <br /> <br /> <br />Trimethoprim - Inhibit folic acid biosynthesis <br />Summary<br />Antibiotics that are active against the cell wall of bacteria include the -lactams, cycloserine, ethionamide, isoniazid, phosphomycin, vancomycin, bacitracin and ristocetin. <br />The β-lactam antibiotics are related structurally in that they all contain a β-lactam ring. These are the penicillins, cephalosporins, monobactams and thienamycins. They are all analogs of d-alanyl-d-alanine. <br />Antibiotics that are active against the bacterial cytoplasmic membrane are polymyxin B and E (colistin). <br />Antibiotics that are active against bacterial DNA are the quinolones (nalidixic acid, norfloxacin and ciprofloxacin), which inhibit DNA gyrase, and metronidazole, which fragments DNA. <br />Antibiotics that block transcription in bacteria are actinomycin D and rifampin. <br />Antibiotics that block translation in bacteria by binding to the 30S ribosome are the aminoglycosides, nitrofurans, spectinomycin and the tetracyclines. <br />The aminoglycoside antibiotics are related structurally in that they all contain a unique aminocyclitol ring structure. These include amikacin, gentamycin, kanamycin, neomycin, streptomycin and tobramycin. <br />Antibiotics that block translation by binding to the 50S ribosome include chloramphenicol, erythromycin, clarithromycin, lincomycin, clindomycin, puromycin, fusidic acid and quinopristin/dalfopristin. <br />The macrolide antibiotics are related structurally in that they all contain a macrocyclic lactone ring of 12-22 carbon atoms, to which one or more sugars are attached. These include erythromycin, clarithromycin, azithrmycin and dirithromycin. <br />Antibiotics that act by inhibiting folic acid biosynthesis include the sulfonamides and trimethoprim. <br />