Mode of action of antibiotics

Disrupting cell wall synthesis

• Targets peptidoglycan cell wall

• Eg. penicillin

  • Bactericidal effect → only effective when bacteria growing and making new cell wall as it disrupts peptidoglycan cell wall synthesis

  • Acts as competitive inhibitor → binds to active site of transpeptidase

  • Inhibit formation of cross-links between tetrapeptides of adjacent chains of peptidoglycans

  • Bacterial cell wall becomes weakened

  • When water enters, high osmotic pressure increases turgor pressure → lyse

Disrupting protein synthesis

• Ribosomes of prokaryotes are 70S while eukaryotes 80S

• Eg. streptomycin: binds to small subunit of bacterial ribosome → initiator tRNA cannot bind

• Eg. tetracycline: blocks aminoacyl-tRNA from attaching to A site

Disrupting nucleic acid synthesis

• Bacterial enzymes diff in conformation to human enzymes (eg. RNA polymerase)

• Eg.rifampin: inhibit RNA synthesis by binding to bacterial RNA polymerase → present transcription

How does antibiotic resistance happen?

• Failure to complete course of antibiotics → some bacteria survive → spontaneous mutation in bacterial population produces antibiotic resistant strain

• transfer of antibiotic-resistance gene from bacterium to bacterium via conjugation/ transduction/ transformation

• When antibiotic given, it acts as a selection pressure

• Bacteria with antibiotic resistance gene survive, reproduce and pass allele to daughter cells

• while those that are susceptible die

• Over a few generations, microevolution → incr in antibiotic resistance allele frequency

Examples of spontaneous mutations that can lead to resistance

Mutations which led to production of enzymes to break down antibiotics, or membrane proteins that inactivate/ pump out antibiotics