Chemotherapy: cellular and molecular mechanisms of antimicrobial agents MCQs With Answer

Chemotherapy: cellular and molecular mechanisms of antimicrobial agents MCQs With Answer

Introduction: This collection of multiple-choice questions focuses on cellular and molecular mechanisms of antimicrobial agents relevant for M.Pharm students. The questions probe drug targets, biochemical pathways, molecular interactions, and clinically important resistance mechanisms—linking pharmacology with microbiology and medicinal chemistry. Emphasis is placed on how antibiotics disrupt cell wall synthesis, protein and nucleic acid metabolism, folate pathways, and membrane integrity, as well as the molecular basis of resistance (enzymatic inactivation, target modification, efflux, and altered permeability). These MCQs are designed to deepen conceptual understanding, prepare for examinations, and support rational selection and development of antimicrobial therapy.

Q1. Which molecular target is primarily inhibited by beta-lactam antibiotics leading to impaired peptidoglycan cross-linking?

• Penicillin-binding proteins (PBPs) involved in peptidoglycan transpeptidation
• D-Ala-D-Ala dipeptide directly in the peptidoglycan chain
• Bacterial DNA gyrase (Topoisomerase II)
• The 30S ribosomal subunit

Correct Answer: Penicillin-binding proteins (PBPs) involved in peptidoglycan transpeptidation

Q2. What is the principal molecular mechanism by which aminoglycosides exert bactericidal activity?

• Irreversible binding to the 30S ribosomal subunit causing misreading of mRNA and mistranslation
• Reversible binding to the 50S subunit blocking peptide bond formation
• Inhibition of folate synthesis by competing with PABA
• Intercalation into DNA causing strand breaks

Correct Answer: Irreversible binding to the 30S ribosomal subunit causing misreading of mRNA and mistranslation

Q3. Vancomycin inhibits cell wall synthesis by which specific molecular interaction?

• Binding to the D-Ala-D-Ala terminus of peptidoglycan precursors, blocking transglycosylation and transpeptidation
• Inhibition of penicillin-binding proteins directly by acylation of active site serine
• Disruption of the cytoplasmic membrane potential by pore formation
• Blocking 30S ribosomal tRNA binding

Correct Answer: Binding to the D-Ala-D-Ala terminus of peptidoglycan precursors, blocking transglycosylation and transpeptidation

Q4. Fluoroquinolones primarily inhibit which bacterial enzyme to block DNA replication?

• DNA gyrase (Topoisomerase II) and, in some organisms, Topoisomerase IV
• DNA-dependent RNA polymerase beta subunit
• Bacterial DNA ligase
• Helicase–primase complex

Correct Answer: DNA gyrase (Topoisomerase II) and, in some organisms, Topoisomerase IV

Q5. Macrolide antibiotics inhibit bacterial protein synthesis by which mechanism?

• Binding to the 23S rRNA of the 50S subunit and blocking translocation
• Blocking the A-site of the 30S ribosomal subunit preventing tRNA entry
• Cleaving peptidyl-tRNA from the ribosome causing premature termination
• Inhibiting formation of N-formylmethionyl-tRNAfMet

Correct Answer: Binding to the 23S rRNA of the 50S subunit and blocking translocation

Q6. Sulfonamides exert antimicrobial action by competitively inhibiting which enzyme in folate biosynthesis?

• Dihydropteroate synthase (DHPS), reducing synthesis of dihydropteroate from PABA
• Dihydrofolate reductase (DHFR), blocking tetrahydrofolate formation
• Thymidylate synthase, preventing dTMP synthesis
• Folylpolyglutamate synthetase, blocking folate retention

Correct Answer: Dihydropteroate synthase (DHPS), reducing synthesis of dihydropteroate from PABA

Q7. Trimethoprim potentiates the antibacterial effect of sulfonamides by inhibiting which enzyme?

• Dihydrofolate reductase (DHFR), preventing reduction of dihydrofolate to tetrahydrofolate
• Folate transporters preventing folate uptake
• Dihydropteroate synthase (DHPS)
• Thymidine kinase

Correct Answer: Dihydrofolate reductase (DHFR), preventing reduction of dihydrofolate to tetrahydrofolate

Q8. Tetracyclines inhibit bacterial protein synthesis primarily by which action?

• Reversibly binding the 30S subunit and blocking attachment of aminoacyl-tRNA to the A site
• Inhibiting peptidyl transferase activity on the 50S subunit
• Inducing premature chain termination by binding mRNA
• Targeting the ribosomal P-site and preventing elongation

Correct Answer: Reversibly binding the 30S subunit and blocking attachment of aminoacyl-tRNA to the A site

Q9. A common plasmid-mediated resistance mechanism against tetracyclines involves which process?

• Active efflux pumps that reduce intracellular antibiotic concentration
• Enzymatic acetylation of the drug rendering it inactive
• Methylation of 23S rRNA preventing drug binding
• Chromosomal mutation of DNA gyrase

Correct Answer: Active efflux pumps that reduce intracellular antibiotic concentration

Q10. According to Ambler classification, which statement correctly describes class A beta-lactamases?

• Class A enzymes are serine beta-lactamases (e.g., TEM, SHV) that hydrolyze penicillins and early cephalosporins
• Class A enzymes are metallo-beta-lactamases requiring zinc for activity (e.g., NDM)
• Class A enzymes are primarily chromosomal cephalosporinases (AmpC)
• Class A enzymes are penicillin-binding proteins modified by mecA

Correct Answer: Class A enzymes are serine beta-lactamases (e.g., TEM, SHV) that hydrolyze penicillins and early cephalosporins

Q11. Daptomycin kills Gram-positive bacteria by which molecular mechanism?

• Inserting into the cytoplasmic membrane, causing rapid depolarization and potassium efflux
• Inhibiting 50S ribosomal translocation
• Blocking peptidoglycan monomer synthesis in the cytoplasm
• Inhibiting DNA gyrase

Correct Answer: Inserting into the cytoplasmic membrane, causing rapid depolarization and potassium efflux

Q12. Polymyxins (e.g., colistin) exhibit bactericidal activity by which cellular action?

• Acting as cationic detergents that bind to lipopolysaccharide (LPS) and disrupt bacterial outer and cytoplasmic membranes
• Inhibiting cell wall transpeptidation by binding PBPs
• Interfering with folate metabolism
• Blocking the 30S ribosomal A-site

Correct Answer: Acting as cationic detergents that bind to lipopolysaccharide (LPS) and disrupt bacterial outer and cytoplasmic membranes

Q13. Linezolid inhibits initiation of bacterial protein synthesis by which molecular mechanism?

• Binding to the 23S rRNA of the 50S subunit and preventing formation of the 70S initiation complex
• Blocking tRNA charging by aminoacyl-tRNA synthetases
• Inhibiting peptide bond formation at the peptidyl transferase center
• Intercalating into DNA to block transcription

Correct Answer: Binding to the 23S rRNA of the 50S subunit and preventing formation of the 70S initiation complex

Q14. Rifampin’s antibacterial action results from inhibition of which enzyme subunit?

• The beta subunit of bacterial DNA-dependent RNA polymerase, blocking transcription initiation
• Bacterial DNA gyrase preventing replication fork progression
• RNA helicase involved in mRNA unwinding
• RNA-dependent DNA polymerase (reverse transcriptase)

Correct Answer: The beta subunit of bacterial DNA-dependent RNA polymerase, blocking transcription initiation

Q15. Methicillin-resistant Staphylococcus aureus (MRSA) expresses mecA gene; how does this confer resistance to beta-lactams?

• mecA encodes PBP2a, a low-affinity penicillin-binding protein with reduced binding to beta-lactams
• mecA encodes a beta-lactamase that hydrolyzes carbapenems
• mecA enhances outer membrane impermeability to beta-lactams
• mecA methylates 23S rRNA preventing antibiotic binding

Correct Answer: mecA encodes PBP2a, a low-affinity penicillin-binding protein with reduced binding to beta-lactams

Q16. What defines the post-antibiotic effect (PAE) relevant to dosing strategies?

• Persistent suppression of bacterial growth after brief exposure to an antibiotic and removal of the drug
• Immediate bactericidal action only while drug concentrations exceed MIC
• Increase in bacterial growth rate after antibiotic exposure
• Drug accumulation inside macrophages leading to prolonged intracellular activity

Correct Answer: Persistent suppression of bacterial growth after brief exposure to an antibiotic and removal of the drug

Q17. How is bactericidal activity quantitatively distinguished from bacteriostatic activity in vitro?

• Bactericidal agents reduce viable count by ≥3 log10 (≈99.9%) over a defined time period, whereas bacteriostatic agents inhibit growth without that reduction
• Bactericidal drugs always have lower MICs than bacteriostatic drugs
• Bactericidal drugs prevent protein synthesis, bacteriostatic drugs disrupt cell walls
• Bactericidal activity is determined by time above MIC only

Correct Answer: Bactericidal agents reduce viable count by ≥3 log10 (≈99.9%) over a defined time period, whereas bacteriostatic agents inhibit growth without that reduction

Q18. Why are beta-lactam and aminoglycoside combinations synergistic against some Gram-negative infections?

• Beta-lactams damage the cell wall and outer membrane, increasing aminoglycoside penetration into the periplasm and cytosol
• Aminoglycosides inhibit DNA synthesis enabling beta-lactams to bind PBPs more effectively
• Both act on the same ribosomal subunit producing additive blockade
• Beta-lactams inhibit efflux pumps allowing more aminoglycoside accumulation

Correct Answer: Beta-lactams damage the cell wall and outer membrane, increasing aminoglycoside penetration into the periplasm and cytosol

Q19. Which genetic mechanism commonly confers macrolide resistance through modification of the antibiotic target?

• Methylation of 23S rRNA by Erm methyltransferases that prevents macrolide binding to the 50S subunit
• Production of extended-spectrum beta-lactamases that hydrolyze macrolides
• Point mutations in DNA gyrase reducing drug uptake
• Acetyltransferase-mediated acetylation of the macrolide lactone ring

Correct Answer: Methylation of 23S rRNA by Erm methyltransferases that prevents macrolide binding to the 50S subunit

Q20. Metronidazole is activated in anaerobic bacteria by reduction to reactive intermediates — what is the primary molecular consequence of these radicals?

• They cause DNA strand breaks and base modifications leading to bacterial cell death
• They inhibit peptidoglycan cross-linking enzymes
• They irreversibly bind to 30S ribosomal RNA stopping translation initiation
• They chelate divalent cations required for enzyme activity

Correct Answer: They cause DNA strand breaks and base modifications leading to bacterial cell death

Download