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    Cell Wall Synthesis Inhibitors

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    Farhana Azmira Asmadi
    1. The document discusses several classes of antibiotics and their mechanisms of action, including beta-lactams, cell wall synthesis inhibitors, protein synthesis inhibitors, nucleic acid synthesis inhibitors, and bacterial membrane disruptors. 2. It provides details on specific antibiotics within each class, their spectra of activity, mechanisms of action, properties, resistance, and side effects. 3. The classes of antibiotics discussed inhibit important bacterial processes like cell wall synthesis, protein synthesis, nucleic acid synthesis, and disrupt bacterial membranes. Understanding their mechanisms of action is important for rational use and to address growing antibiotic resistance.

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    Cell Wall Synthesis Inhibitors

    Uploaded by

    Farhana Azmira Asmadi
    52 views5 pages
    1. The document discusses several classes of antibiotics and their mechanisms of action, including beta-lactams, cell wall synthesis inhibitors, protein synthesis inhibitors, nucleic acid synthesis inhibitors, and bacterial membrane disruptors. 2. It provides details on specific antibiotics within each class, their spectra of activity, mechanisms of action, properties, resistance, and side effects. 3. The classes of antibiotics discussed inhibit important bacterial processes like cell wall synthesis, protein synthesis, nucleic acid synthesis, and disrupt bacterial membranes. Understanding their mechanisms of action is important for rational use and to address growing antibiotic resistance.

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    medical microbiology

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    1. The document discusses several classes of antibiotics and their mechanisms of action, including beta-lactams, cell wall synthesis inhibitors, protein synthesis inhibitors, nucleic acid synthesis inhibitors, and bacterial membrane disruptors. 2. It provides details on specific antibiotics within each class, their spectra of activity, mechanisms of action, properties, resistance, and side effects. 3. The classes of antibiotics discussed inhibit important bacterial processes like cell wall synthesis, protein synthesis, nucleic acid synthesis, and disrupt bacterial membranes. Understanding their mechanisms of action is important for rational use and to address growing antibiotic resistance.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as DOCX, PDF, TXT or read online from Scribd
    Download as docx, pdf, or txt
    52 views5 pages

    Cell Wall Synthesis Inhibitors

    Uploaded by

    Farhana Azmira Asmadi
    1. The document discusses several classes of antibiotics and their mechanisms of action, including beta-lactams, cell wall synthesis inhibitors, protein synthesis inhibitors, nucleic acid synthesis inhibitors, and bacterial membrane disruptors. 2. It provides details on specific antibiotics within each class, their spectra of activity, mechanisms of action, properties, resistance, and side effects. 3. The classes of antibiotics discussed inhibit important bacterial processes like cell wall synthesis, protein synthesis, nucleic acid synthesis, and disrupt bacterial membranes. Understanding their mechanisms of action is important for rational use and to address growing antibiotic resistance.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as DOCX, PDF, TXT or read online from Scribd
    Download as docx, pdf, or txt
    of 5

    1.

    BETA-LACTAMS Penicillin Type s Natural & Synthetic Binds to enzymes that cross-link peptidoglycansubunits An enzyme called transpeptidase(type of penicillin binding protein) forms the covalent bond between peptide side chains, with release of a terminal D-alanine-Penicillin binds and inhibits this enzyme As the cell wall continues to be formed, the lack of covalent bonds between the peptide side chains eventually results in cell lysis; breakage 2. 1. Cephalosporin

    CELL WALL SYNTHESIS INHIBITORS OTHER Cycloserine Bacitracin

    GLYCOPEPTIDASE Eg: Vancomycin

    Blocking the transpeptidationreaction (forming the peptide crosslinks) By binding to the D-alanylD-alanineportion of the p entapeptidesidechain. This prevents formation of the covalent crosslinksbetween adjacent glycanchains. Similar to betalactamexcept beta lactamdrugs bind to the transpeptidaseenzyme itself Blocking the transgylcosylationreaction (elongating the glycanchains) large molecules that bind to cell wall precursors acts as a stericimpediment Result: Leads to structurally weakened cell wall until the cell lyses only active against G +veorganisms too large to cross G vecell wall

    Mode of actions

    Blocks synthesis of peptidoglycanprecursors by: inhibiting the conversion of L-alanineto D-alanine preventing the formation of the D-alanyl-Dalaninerequired for peptide side chain formation

    Prevents regeneration of carrier molecule required for peptidoglycansynthesis by Inhibiting the enzyme pyrophosphatasethat removes the terminal phosphate from bactoprenolpyrophosphate (carrier molecule). Without removal of the terminal phosphate, bactoprenolcannot be used again to transport cell-wall precursors through the cell membrane

    Only effective against growingbacteria no effect on stationary phase cells Not effective against species without cell walls (mycoplasma) with impenetrable cell walls (mycobacteria) That live as intracellular pathogens (Chlamydia) Beware penicillin allergy Least toxic of antibiotics From rash (25%) to anaphylactic shock (0.04% of cases)

    Improved activity against Gram-verods Broad-spectrum For patients allergic to penicillin Although 10% of patients allergic to penicillin also allergic to cephalosporin Has it own side effects: thrombophlebitis, GIT disturbance

    side effects: confusion, coma, liver damage Second-line drug for TB treatment

    Topical use only (can cause kidney & liver damage) Effective against G +ve(Staphylococciand Streptococci)

    Properties

    Aminoglycosides bind to 30S ribosome and can Affect initiation Misreading of genetic code o Wrong amino acid inserted o Causes the membrane to damage and bact. Dies. not absorbed from gut, often IV infusion Ineffective against anaerobes as transport of drug into cell requires oxygen resistance due to altered cell permeability or 30S binding site Streptomycin bactericidal, used to treat tuberculousmeningitis Side Effects: hearing loss (irreversible) and renal damage if taken for prolonged periods Resistance Production of enzyme to prevent binding to ribosome Binding site on ribosome changes Neomycin used topically very toxic if used systematically Gentamicin active against many G ve

    Tetracyclines Binds reversibly to 30S ribosomal subunit distort A site, prevent tRNAfrom binding i.e. prevent tRNAfrom entering acceptor site on the ribosome Broad spectrum, bacteriostatic(reversible binding) suppress normal gut flora GI disturbance o diarrhea and overgrowth of drug-resistant bacteria and fungi also bind to eukaryotic ribosomes(less efficiently) affect development of bones and teeth o Brown staining of teeth deposition of drug as tetis a calcium chelator not suitable for children, pregnant women Resistance usually alteration of cell membrane to exclude drug

    PROTEIN SYNTHESIS INHIBITOR Chloramphenicol

    Microlides (Erythromycin)

    Lincosamides

    Mode of Action

    binds to 50S subunit, inhibits peptide bond formation blocks elongation

    binds to 50S ribosome, blocks the translocation step by preventing the release of the uncharged (or empty) tRNAfrom the donor site after the peptide bond is formed

    Properties

    Commonly bacteriostatic, bacteriocidalto S. pneumoniae, H. influenzaeand N. meningitides broad spectrum, can kill even anaerobic bacteria However can cause GI disturbance, overgrowth of C. albicans can occur small, polar; so oral administration possible crosses blood-brain barrier used to treat bacterial meningitis toxicity and resistance limit usefulness of drug Potential side-effects: Bone marrow toxicity (but reversible) and aplastic anemia toxic to neonates (immature liver) Grey baby syndrome

    bacteriostatic, most active against G+vecells alternative to penicillin, especially for Strep infection side effects are mild, may cause nausea Resistance: due to altered ribosomaltarget site

    active against anaerobes; penetrates bone useful for osteomyelitis Serious side effect potentially fatal pseudomembranousc olitis Caused by overgrowth of Clostridium difficilewhich produces necrotizing toxins C. difficileovergrows because it is always resistant to clindamycin

    resistance common primarily due to enzymatic modification that prevents drug binding to ribosome

    Antibiotic Aminoglycoside s

    Ribosomal Subunit 30S

    Mode of Action Blocks functioning of initiation complex and causes misreading of mRNA

    Bactericidal or Bacteriostatic Bactericidal

    Side Effects

    Resistance due to altered cell permeability or 30S binding site

    Tetracyclines

    30S

    Blocks tRNAbinding to ribosome

    Bacteriostatic

    Chloramphenic ol

    50S

    Blocks peptidyltransferase

    Both

    Erythromycin

    50S

    Blocks translocation

    Primarily Bacteriostatic Primarily bacteriostatic

    diarrhea and overgrowth of drugresistant bacteria and fungi affect development of alteration of cell membrane to bones and teeth o Brown staining exclude drug of teeth deposition of drug as tetis a calcium chelator enzymatic Bone marrow toxicity (but modification that reversible) and prevents drug aplasticanemia binding to ribosome due to altered Nausea ribosomaltarget site potentially fatal pseudomembranouscolitis

    Clindamycin

    50S

    Blocks translocation

    3. NUCLEIC ACID SYNTHESIS INHIBITORS DNA synthesis (replication) inhibitors Quinolones

    Properties synthetic chemotherapeutic agents inactivate bacterial gyrase(= DNA topoisomeraseII) and topoisomerase enzymes that wind and unwind DNA dont bind to mammalian enzymes, minimal toxicity Resistance: due to alterations in DNA gyraseor cell membrane permeability for G-veenteric bacteria; sometimes used for UTI

    Naladixic Acid

    Fluoroquinolones have broader spectrum of activity (G +ve, G -ve, anaerobes)

    RNA synthesis (transcription) inhibitors

    Properties Rifampicin(Rifampin) o inactivates RNA polymerase, blocks mRNA synthesis - broad spectrum (GI disturbance) - effective against Mycobacterium tuberculosis - occasional side effects: liver damage, allergic reactions Resistance increasing o due to mutation of binding site on RNA polymerase Rifampicinis usually given in combination with other drugs because resistant mutants appear at a high rate when used alone

    Rifamycins

    Nucleotide synthesis inhibitors

    Properties analogues of para-aminobenzoicacid (PABA), a precursor of tetrahydrofolicacid (THFA) o required for nucleotide synthesis in bacteria (mammals obtain THFA in diet) o competitive inhibitor, so bacteriostatic o active against G ve, so good for UTIs but resistance widespread

    Sulfonamides

    Trimethoprim Co-trimoxazole

    acts at a later point in nucleotide synthesis pathway = Trimethoprim + sulfamethoxazole (sulfonamide) synergistic drug interaction; resistance less likely useful for long term prophylaxis of UTIs

    4. BACTERIAL MEMBRANE DISRUPTORS depolarisebacterial membranes affect membrane transport processes, ATP synthesis Daptyomycinis useful against MRSA, VRE bactericidal, detergent-like action active against most G-veorganisms toxic to kidney and neural tissues topical use for G veinfections

    Lipopeptides

    Polymyxin B

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