Questions: 24. How do drugs target bacterial cells? For example, what is the mechanism of action (or main target) of the fluoroquinolones, penicillin, sulfa drugs, fosfomycin, macrolides, aminoglycosides, metronidazole...? 25. What are mechanisms of antibiotic resistance? How can antibiotics be modified to counteract some mechanisms of resistance?

Certainly! Let's address the first question regarding how drugs target bacterial cells and the mechanisms of action for specific antibiotics:

Antibiotics target bacterial cells by interfering with essential bacterial processes. Here are the mechanisms of action for the specified antibiotics:

1. Fluoroquinolones:

   • Mechanism: Inhibit bacterial DNA gyrase and topoisomerase IV, enzymes critical for DNA replication and transcription.
   • Target: DNA synthesis.

2. Penicillin:

   • Mechanism: Inhibits the synthesis of bacterial cell walls by binding to penicillin-binding proteins (PBPs), which are involved in the cross-linking of the peptidoglycan layer.
   • Target: Cell wall synthesis.

3. Sulfa Drugs (Sulfonamides):

   • Mechanism: Inhibit dihydropteroate synthase, an enzyme involved in the synthesis of folic acid, which is necessary for DNA and RNA synthesis.
   • Target: Folic acid synthesis.

4. Fosfomycin:

   • Mechanism: Inhibits the enzyme MurA, which is involved in the first step of peptidoglycan biosynthesis.
   • Target: Cell wall synthesis.

5. Macrolides:

   • Mechanism: Bind to the 50S subunit of the bacterial ribosome, inhibiting protein synthesis by blocking the exit tunnel of the nascent peptide.
   • Target: Protein synthesis.

6. Aminoglycosides:

   • Mechanism: Bind to the 30S subunit of the bacterial ribosome, causing misreading of mRNA and inhibiting protein synthesis.
   • Target: Protein synthesis.

7. Metronidazole:

   • Mechanism: Undergoes reduction in anaerobic bacteria and protozoa to form reactive intermediates that damage DNA.
   • Target: DNA integrity.

These antibiotics exploit differences between bacterial and human cells, allowing them to selectively target bacteria without harming human cells.