Antimicrobials: Cell Targets & Mechanisms

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Questions and Answers

Beta-lactams are a class of antibiotics that inhibit bacterial growth by directly interfering with which cellular process?

  • Replication of bacterial DNA
  • Synthesis of mycolic acid in the cell wall
  • Transpeptidation during cell wall synthesis (correct)
  • Ribosomal RNA within the 30S subunit

Glycopeptide antibiotics, such as Vancomycin, are effective against Gram-positive bacteria because they primarily target:

  • The outer membrane porins to disrupt membrane integrity
  • The synthesis of 23S rRNA in the 50S ribosomal subunit
  • The D-ala-D-ala stem of peptidoglycan precursors (correct)
  • The activity of DNA gyrase, preventing DNA supercoiling

Lipopeptide antibiotics, exemplified by Daptomycin, disrupt bacterial cell membrane integrity through:

  • Blocking the binding of tRNA to the 16S rRNA
  • Inhibition of RNA polymerase beta subunit
  • Interference with the production of tetrahydrofolate
  • Depolarization of the cell membrane (correct)

Polymyxins are known for their activity against Gram-negative bacteria. Their mechanism of action involves:

<p>Binding to lipopolysaccharide (LPS) and inserting into the bacterial membranes (A)</p> Signup and view all the answers

Aminoglycosides are a class of antibiotics that interfere with protein synthesis by:

<p>Binding to the 16S rRNA in the 30S ribosomal subunit (A)</p> Signup and view all the answers

Tetracyclines inhibit bacterial protein synthesis by specifically:

<p>Blocking the binding of aminoacyl-tRNA to the A-site of the ribosome (A)</p> Signup and view all the answers

Macrolide antibiotics, such as Erythromycin, target protein synthesis by interacting with:

<p>The 23S rRNA in the 50S ribosomal subunit (B)</p> Signup and view all the answers

Oxazolidinones, like Linezolid, are effective against Gram-positive bacteria because they inhibit protein synthesis by:

<p>Preventing the formation of the 70S initiation complex (A)</p> Signup and view all the answers

Fluoroquinolones are a class of antibiotics that target bacterial DNA replication by:

<p>Binding to and inhibiting DNA gyrase (C)</p> Signup and view all the answers

Metronidazole is specifically effective against anaerobic bacteria because its mechanism of action involves:

<p>Nicking of bacterial DNA after reduction in anaerobic conditions (C)</p> Signup and view all the answers

Rifampin is an antibiotic that inhibits bacterial transcription by targeting:

<p>The β subunit of RNA polymerase (B)</p> Signup and view all the answers

Sulfonamide antibiotics inhibit the synthesis of tetrahydrofolate by acting as a competitive inhibitor of:

<p>Para-aminobenzoic acid (PABA) in dihydrofolate synthesis (B)</p> Signup and view all the answers

Trimethoprim, often used in combination with sulfamethoxazole, also targets tetrahydrofolate synthesis by inhibiting:

<p>Dihydrofolate reductase (C)</p> Signup and view all the answers

Isoniazid, a pro-drug used to treat Mycobacterium tuberculosis, primarily targets:

<p>Mycolic acid synthesis (C)</p> Signup and view all the answers

Nitroimidazole antibiotics, similar to Isoniazid in their target pathway against Mycobacterium tuberculosis, also inhibit:

<p>Mycolic acid synthesis (B)</p> Signup and view all the answers

Diarylquinoline drugs, such as Bedaquiline, are used to treat tuberculosis by specifically inhibiting:

<p>ATP synthase (C)</p> Signup and view all the answers

Resistance to beta-lactam antibiotics is commonly mediated by bacterial mechanisms including:

<p>Production of β-lactamase enzymes (A)</p> Signup and view all the answers

The spectrum of activity for Beta-lactam antibiotics is generally described as:

<p>Effective against both Gram-positive and Gram-negative bacteria (G+/-) (A)</p> Signup and view all the answers

Which of the following is an example of a Glycopeptide antibiotic?

<p>Vancomycin (A)</p> Signup and view all the answers

Macrolide antibiotics are known to have a broad spectrum of activity, but are particularly noted for their effectiveness against:

<p>A broad range of bacteria including Gram-positive, Gram-negative, and some atypical bacteria (C)</p> Signup and view all the answers

Flashcards

Beta-lactams Mechanism

Inhibit transpeptidation by inactivating cell wall transpeptidases.

Examples of Beta-lactams

Penicillin, Cephalosporin, Carbapenem, Monobactam.

Glycopeptides/Lipoglycopeptides Mechanism

Inhibit transpeptidation by binding to D-ala-D-ala stem.

Examples of Glycopeptides/Lipoglycopeptides

Vancomycin, Dalbavancin, Oritavancin.

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Lipopeptides Mechanism

Membrane depolarization.

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Example of Lipopeptides

Daptomycin.

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Polymyxins Mechanism

Binds LPS, inserts into OM and IM of Gram-negative.

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Example of Polymyxins

An example: Colistin

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Aminoglycosides Mechanism

Binds 16S rRNA in 30S ribosomal subunit.

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Example of Aminoglycosides

Gentamicin.

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Tetracyclines Mechanism

Binds 16S rRNA in 30S ribosomal subunit.

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Examples of Tetracyclines

Doxycycline, Tigecycline.

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Macrolides Mechanism

Binds 23S rRNA in 50S ribosomal subunit.

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Example of Macrolides

Erythromycin.

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Oxazolidinones Mechanism

Binds 23S rRNA in 50S ribosomal subunit.

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Example of Oxazolidinones

Linezolid.

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Fluoroquinolones Mechanism

Binds DNA gyrase.

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Example of Fluoroquinolones

Ciprofloxacin.

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Isoniazid (Pro-Drug) and Nitroimidazole Mechanism

Inhibits Mycolic acid synthesis.

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Example of Diarylquinoline

Bedaquiline.

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Study Notes

  • Study notes on cell target, class, mechanism, spectrum, resistance, and examples of antimicrobials

Cell Wall

  • Beta-lactams inhibit transpeptidation by inactivating cell wall transpeptidases, effective against Gram-positive and Gram-negative bacteria (G+/G-).
    • Resistance mechanisms: OM barrier, efflux, β-lactamase production, and target modification (PBPs).
    • Examples: Penicillin, Cephalosporin, Carbapenem, and Monobactam.
  • Glycopeptides and Lipoglycopeptides inhibit transpeptidation by binding to the D-ala-D-ala stem, primarily effective against Gram-positive bacteria (G+).
    • Resistance mechanisms: OM barrier and D-ala-D-lac substitute.
    • Examples: Vancomycin, Dalbavancin, and Oritavancin.

Cell Membrane

  • Lipopeptides cause membrane depolarization, effective against Gram-positive bacteria (G+).
    • Resistance mechanism involves membrane alteration.
    • Example: Daptomycin.
  • Polymyxins bind LPS and insert into the outer (OM) and inner membranes (IM) of Gram-negative bacteria (G-).
    • Resistance mechanisms: LPS modification and efflux.
    • Example: Colistin.

Protein Synthesis

  • Aminoglycosides bind to 16S rRNA in the 30S ribosomal subunit, exhibiting broad-spectrum activity.
    • Resistance mechanisms: Antibiotic inactivation and efflux.
    • Example: Gentamicin.
  • Tetracyclines bind to 16S rRNA in the 30S ribosomal subunit, showing broad-spectrum activity.
    • Resistance mechanisms: Efflux and ribosome protection.
    • Examples: Doxycycline and Tigecycline.
  • Macrolides bind to 23S rRNA in the 50S ribosomal subunit, exhibiting broad-spectrum activity.
    • Resistance mechanisms: Efflux and 23S rRNA methylation.
    • Example: Erythromycin.
  • Oxazolidinones bind to 23S rRNA in the 50S ribosomal subunit, effective against Gram-positive bacteria (G+).
    • Resistance mechanisms: Efflux and 23S rRNA methylation.
    • Example: Linezolid.

DNA Replication

  • Fluoroquinolones bind to DNA gyrase, displaying broad-spectrum activity.
    • Resistance mechanisms: Efflux and gyrase mutation.
    • Example: Ciprofloxacin.
  • Metronidazole nicks bacterial DNA, effective against anaerobic bacteria.
    • Resistance mechanisms: Failure to activate and reduction in flavodoxin expression.
    • Example: Flagyl.

Transcription

  • Rifampin binds to the β subunit of RNA polymerase, exhibiting broad-spectrum activity.
    • Resistance mechanisms: RNA polymerase mutation and efflux.
    • Example: Rifampicin.
  • Macrocyclic Macrolides inhibit RNA polymerase, effective against C. difficile.
    • Resistance: None reported yet
    • Example: Difficid

Tetrahydrofolate

  • Sulfonamides inhibit PABA to FHâ‚‚ (PABA mimic), displaying broad-spectrum activity.
    • Resistance mechanisms: Enzyme mutation and efflux.
    • Examples: Bactrim and Septra.
  • Trimethoprim inhibits FHâ‚‚ to FHâ‚„ (FHâ‚‚ mimic), exhibiting broad-spectrum activity.
    • Resistance mechanisms: Enzyme mutation and efflux.
    • Examples: Bactrim and Septra.

Mycolic Acid

  • Isoniazid (Pro-Drug) inhibits mycolic acid synthesis, effective against Mycobacterium tuberculosis (M. tb.).
    • Resistance mechanism: Failure to activate, KatA.
    • Example: Isoniazid.
  • Nitroimidazole inhibits mycolic acid synthesis, effective against M. tb.
    • Example: Pretomanid

ATP Synthase

  • Diarylquinoline inhibits ATP synthase, effective against M. tb.
    • Example: Bedaquiline.

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