MI04 - Antibiotics and Resistance

What defines a good antibiotic target?

A good target is unique to bacteria, essential for survival, and absent or very different in the host (e.g., peptidoglycan, bacterial ribosomes). This ensures selective toxicity.

What is selective toxicity?

Greater harm to microbes than to host cells, achieved by targeting unique microbial structures or processes.

What is therapeutic index?

The ratio of the lowest dose toxic to the host to the dose required to kill the microorganism. A higher therapeutic index means a safer drug.

What is the difference between broad-spectrum and narrow-spectrum antibiotics?

• Broad-spectrum: active against many bacterial types (Gram+ and Gram-).

• Narrow-spectrum: active against a few, closely related bacteria.

What is the difference between bacteriostatic and bactericidal antibiotics?

• Bacteriostatic: inhibits growth.

• Bactericidal: kills bacteria.

What are some adverse effects of antibiotics?

Allergic reactions (e.g., penicillin), toxicity (teeth, hearing, blood systems, mitochondria), disruption of normal microbiota (C. difficile/colitis)

How is antibiotic sensitivity measured?

By determining MIC (minimum inhibitory concentration), MLC (minimum lethal concentration), and zone of inhibition (disc diffusion assay).

What is MIC vs. MLC?

• MIC: lowest concentration that inhibits bacterial growth.

• MLC: lowest concentration that kills the bacteria.

How do penicillins work?

They inhibit cell wall synthesis by blocking the cross-linking of peptidoglycan.

What is a beta-lactam?

A chemical structure (beta-lactam ring) in penicillins and related drugs, essential for blocking the cross-linking of peptidoglycan.

What is beta-lactamase?

An enzyme (penicillinase) produced by bacteria that cleaves the beta-lactam ring, inactivating the antibiotic.

What is Augmentin?

Amoxicillin + clavulanic acid (a beta-lactamase inhibitor).

What are cephalosporins?

Beta-lactam antibiotics that are more resistant to penicillinases.

What are advantages of cephalosporins over penicillins?

They are broader spectrum and resistant to some beta-lactamases.

What are carbapenems?

Broad-spectrum beta-lactam antibiotics that inhibit cell wall synthesis and resist many beta-lactamases (e.g., imipenem).

What activities do carbapenems possess?

Both anti-peptidoglycan synthesis activity and beta-lactamase inhibitor activity.

Give examples of protein synthesis-inhibiting antibiotics.

Tetracyclines (doxycycline), chloramphenicol, aminoglycosides (streptomycin, gentamicin), macrolides (erythromycin), lincosamides (clindamycin).

What is chloramphenicol used for, and what are its risks?

Last-resort for meningitis; risk of aplastic anemia.

Which antibiotic can cause deafness as a side effect?

Streptomycin (aminoglycoside).

What are polypeptide antibiotics and their actions?

• Polymyxin B: disrupts bacterial membranes.

• Bacitracin: blocks secretion of peptidoglycan precursors.

What is rifampin?

Antibiotic that binds RNA polymerase and inhibits mRNA synthesis.

Which antibiotics inhibit DNA synthesis?

Nalidixic acid, fluoroquinolones (ciprofloxacin), novobiocin (target DNA gyrase).

What is metronidazole?

An antibiotic specific for anaerobes (Flagyl); disrupts electron transport and causes DNA damage. Activated only under anaerobic conditions.

Which antibiotics inhibit folic acid synthesis?

Trimethoprim and sulfonamides (Bactrim = trimethoprim + sulfamethoxazole).

What are common mechanisms of antibiotic resistance?

• Impermeability (drug cannot enter cell)

• Altered binding site (drug cannot bind)

• Alternative pathways (bypass inhibition)

• Inactivation of drug (enzymes like beta-lactamase)

• Efflux pumps (pump drug out of cell)

How fast does drug resistance emerge after antibiotic introduction?

Usually within 5–10 years.

What is MRSA’s resistance mechanism?

Produces MecA protein (PBP2a), an altered penicillin-binding protein that prevents binding of beta-lactams.

What are defensins?

Host antimicrobial peptides that disrupt microbial membranes; part of innate immunity.

What are the main classifications of antibiotics by pathogen type?

Antibacterial, antifungal, antiparasitic/antiprotozoan, and antiviral.

What are antibiotic generations?

• First generation: naturally produced by organisms.

• Second/third generation: semi-synthetic, modified from natural forms.

• Newer: computer-designed antibiotics built on natural structures.

What is a broth dilution assay used for?

To determine MIC (minimum inhibitory concentration).

What are the five main bacterial targets of antibiotics?

Cell wall synthesis, protein synthesis, nucleic acid synthesis, metabolic pathways, and cell membranes.

What are common treatments for bacterial conjunctivitis (“pink eye”)?

Erythromycin, gentamicin, tobramycin, ciprofloxacin (eye drops) and erythromycin ointment.

What are some drivers of antibiotic resistance spread?

Overuse of antimicrobial hand soaps (triclosan), antibiotic use in farm animals, R plasmids spreading resistance, and spontaneous mutations.

What was triclosan used for and why was it banned?

It was used in hand soaps; it was banned in the US because it promoted disinfectant-resistant bacteria.

What is the role of R plasmids in antibiotic resistance?

They spread resistance genes between bacteria via horizontal transfer.

What are examples of antibiotic inactivation?

Beta-lactamase cleaves penicillins; chemical modification of chloramphenicol.