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Antibiotics: Bacterial Protein Synthesis Inhibitors - Coggle Diagram

- - - - IV
      - or IM
      - block initiation of translation & causes misreading of mRNA
    - - Quinupristin (streptogramin B) and dalfopristin (streptogramin A) work synergistically by binding sequentially to the 50S ribosomal subunit
        
        SA prevents binding of amino acyl-tRNA; SB inhibits peptide-elongation, releases peptidyl-tRNA
        
        Dalfopristin (streptogramin A) alters the 50S ribosomal subunit shape. This facilitates binding of quinupristin (streptogramin B). Dalfopristin also binds to the ribosome preventing early peptide transferase mediated elongation of the peptide chain. Quinupristin blocks later extension of peptide chains. The combined result is production of incomplete peptide chains
      - 30:70 ratio to synergistically treat multidrug-resistant gram (+) bacteria
      - IV
      - considerations
        
        inhibit liver CYP3A4 that metabolizes cyclosporine
      - 50S subunit inhibitor
    - - Translation Inhibitors
  - - - Fidaxomixin
        
        Side effects
        
        GI side effects, hypersensitivity reactions, anemia and neutropenia.
        
        GI infections
        
        Fecal excretions
        
        inhibits bacterial protein synthesis by binding the sigma (σ) submit of bacterial DNA-dependent RNA polymerase.
    - - Rifaximin
        
        tuberculosis
        
        Inhibits bacterial protein synthesis by binding the beta (β) subunit of ...
        
        caution in patients with hepatic impairment (cyt p450)
  - - - Monic Acid + 9-hydroxynonaoic acid
  - - - Metronidazole – Mechanism of Action (High-Yield)
        
        Passive diffusion into microbial cells.
        
        In anaerobic organisms, reduced electron carriers (e.g., ferredoxin) donate electrons to metronidazole’s nitro group (-NO₂).
        
        This generates toxic nitro radical anions, which:
        
        Fragment DNA
        
        Destabilize the double helix
        
        Damage proteins → cell death (bactericidal/protozoacidal)
        
        In aerobic conditions, oxygen competes for electrons and re-oxidizes the radical intermediates, preventing activation.
        
        Selectivity: Only effective against anaerobic bacteria & protozoa; minimal effect on aerobes or human cells.
    - - TMP-SMX
        
        TMP inhibits tetrahydrofolic acid formation
        
        SMX impairs bacterial folate synthesis
        
        Treats: Pneumocystis jirovecii pneumoniae, Nocardia spp. and toxoplasmosis (T. gondii)
    - - causes formation of bactericidal intermediate
    - - Side effects
        
        QT prolongation
      - Gram - bacteria
        
        DNA Gyrase inhibitor
        
        Gyrase introduces negative supercoils into DNA, a process requiring ATP hydrolysis. It plays a critical role in managing DNA's topological strain
      - Gram + Bacteria
        
        topoisomerase inhibitor
  - - - Beta-lactam
        
        Inhibits by bind PBP domain
        
        Cephalosporins
        
        Carbapenems
        
        Monobactams
        
        Penicillins
        
        D-Ala cell wall inhibitor
        
        Vancomycin
    - - Daptomycin
      - Polymixins
      - Bacitran
- - - - 30S
      - block attachment of tRNA to the 30s segment of ribosome (specifically binds 16 ribosomal aminoacyl site)
  - - - 50S
      - Macrolides bind reversibly to the 23S RNA domain 5 of the 50S ribosomal subunit exit tunnel
      - azithromycin
    - - binds to the same location on the 50S ribosomal subunit as macrolides
      - eg. clindamycin
        
        resitstance
        
        methylation of 23s ribosomal RNA of the 50S subunit
    - - reversibly to the 50S ribosomal subunit and inhibits bacterial peptidyl transferase
      - Side effects:
        
        Gray baby syndrome
        
        Premature babies are deficient in UDP-glucuronosyltransferase
        
        Symptoms include ashen gray skin, cardiorespiratory depression, lethargy, and vomiting
        
        UDP-glucuronosyltransferase (UGT) is a key enzyme in the phase II metabolism pathway, specifically glucuronidation
        Phase II reaction: Conjugation → attachment of glucuronic acid (from UDP-glucuronic acid) to substrates.
        
        can cause dose-dependent anemia, leukopenia, and thrombocytopenia
        
        potentially fatal aplastic autoimmune anemia.
    - - Linezolid
        
        inhibits an earlier stage of bacterial protein synthesis than other protein synthesis inhibitor antibiotics. It binds to a location on the 23S ribosomal RNA of the 50S subunit at the interface between the 50S and 30S subunits
        
        prevents formation of the 70S initiation complex that includes mRNA, fmet-tRNA and the 30S ribosomal subunit required for bacterial translation.
        
        results in minimal cross-resistance with other drugs. Reports of linezolid resistance are minimal
        
        Side effects
        
        neuropathy
        
        reversible myelosuppression
        
        Serotonin Syndrome
    - - lefamulin
        
        association of lefamulin with the 50S subunit causes the binding pocket to close around lefamulin