PH3115 Unit 3 antibiotics

Why are antibiotic targets limited and why is this important?

Only ~10–15 bacterial targets exist → resistance is inevitable

What is MIC (minimum inhibitory concentration)?

Lowest concentration of antibiotic preventing visible bacterial growth

What are the clinical categories of antibiotic susceptibility?

Susceptible (likely success); Intermediate (uncertain); Resistant (likely failure)

What are the main targets of antibiotics in bacteria?

Cell wall, protein synthesis (30S/50S), DNA gyrase, RNA polymerase, cell membrane, folate metabolism

What is the difference between intrinsic and acquired resistance?

Intrinsic = natural property; Acquired = mutation or gene transfer

How do β-lactam antibiotics work?

Bind PBPs → inhibit transpeptidation → prevent peptidoglycan cross-linking → cell death

How do glycopeptide antibiotics work?

Bind D-Ala-D-Ala → block peptidoglycan elongation

How does bacitracin inhibit cell wall synthesis?

Blocks lipid carrier → prevents transport of cell wall precursors (stage 2)

How does cycloserine inhibit cell wall synthesis?

Inhibits D-alanine incorporation → blocks precursor formation (stage 1)

Which ribosomal subunit do tetracyclines act on and what do they do?

Bind 30S → block aminoacyl-tRNA binding to A site

How do aminoglycosides inhibit protein synthesis?

Bind 30S irreversibly → inhibit translocation + cause misreading → bactericidal

How do macrolides (MLS) inhibit protein synthesis?

Bind 50S → block translocation → cause premature peptide release

How does chloramphenicol inhibit protein synthesis?

Inhibits peptidyl transferase → blocks peptide bond formation

How does linezolid inhibit protein synthesis?

Blocks initiation of translation on 50S ribosome

How does mupirocin inhibit protein synthesis?

Inhibits isoleucyl-tRNA synthetase

How do quinolones inhibit bacterial DNA replication?

Stabilise tertiary drug-enzyme-DNA complexes and stranded break → prevent DNA re-ligation → block replication

How do rifamycins inhibit transcription?

Inhibit RNA polymerase → block RNA synthesis initiation

How do polymyxins affect bacterial cells?

Bind LPS (lipopolysaccharides) of gram -ve → disrupt membrane → increase permeability → bactericidal

How does daptomycin work?

Causes membrane depolarisation → inhibits DNA, RNA and protein synthesis

How do sulphonamides inhibit bacterial growth?

Compete with PABA → inhibit dihydropteroate synthase (DHPS) → reduce folic acid synthesis

How does trimethoprim inhibit bacterial growth?

Inhibits dihydrofolate reductase (DHFR)

How do bacteria develop resistance via reduced permeability?

Alter membrane or porins → decrease antibiotic entry

What is efflux-mediated antibiotic resistance?

Active pumps remove antibiotic → reduce intracellular concentration

How do bacteria inactivate β-lactam antibiotics?

β-lactamases hydrolyse β-lactam ring

How do bacteria enzymatically inactivate aminoglycosides?

Use acetyltransferases, phosphotransferases, adenyltransferases

How is chloramphenicol resistance mediated?

Chloramphenicol acetyltransferase inactivates drug

What is target site modification in antibiotic resistance?

Altered binding site → reduced antibiotic affinity

How do bacteria resist β-lactams via target modification?

Produce altered PBPs (e.g. mecA in MRSA)

How do bacteria resist glycopeptides like vancomycin?

Replace D-Ala-D-Ala with D-Ala-D-Lac → reduced binding

How do bacteria resist macrolides?

Methylation of 23S rRNA → reduced binding

How do bacteria resist quinolones?

Mutations in DNA gyrase (QRDR) reduce binding

How do bacteria bypass folate pathway inhibition?

Mutate DHFR/DHPS or increase PABA production

What is target amplification resistance?

Increased production of target enzyme reduces drug effect

Why does cross-resistance occur within antibiotic classes?

Same mechanism or target → one mutation affects multiple drugs

Why are many protein synthesis inhibitors bacteriostatic?

They inhibit growth rather than killing bacteria directly