Chapter 20 Antibacterial Agents Medical Microbiology Chapter 20 Antibacterial Agents

Antimicrobial Agents Antibacterial agent - chemical that kills or inhibits the growth of microorganisms at a very low concentration Protosil (sulfanilamide) in 1935 Antimicrobial agents produced by living organisms are called antibiotics Fleming’s discovery of penicillin

Antibiotics Important Properties: Selective toxicity Broad-spectrum vs. narrow-spectrum drugs

Targets of Antimicrobial Drugs Antibiotics have one of the following targets: Inhibition of cell wall synthesis Disruption of the bacterial membrane Inhibition of protein synthesis Inhibition of nucleic acid synthesis Antimetabolites Figure 20-1

Inhibition of cell wall synthesis Beta-lactams (penicillins, cephalosporins, etc.) inhibit the enzymes required to build peptidoglycan structure of the cell wall - Barrel analogy Penicillin inhibits the formation of the peptide links

Inhibition of cell wall synthesis Vancomycin – only effective against Gram + Isoniazid, ethambutol, and others are only effective against Mycobacteria Others – Figure 20-1 and Tables 20-2, 20-3, and 20-4

Damage to Membranes Damage to Membranes – Polymixin antibiotics Only used topically because of toxicity

Inhibition of protein synthesis Aminoglycosides – bind to the 30S sub-unit and cause: Misreading of mRNA Early termination of translation Table 20-5 Tetracyclines – bind to the 30S sub-unit and block tRNA binding Table 20-6

Inhibition of protein synthesis Others Table 20-6 and Figure 20-1

Inhibition of nucleic acid synthesis Quinolones – inhibit DNA replication enzymes (gyrase) Ciprofloxicin and others Table 20-7 Rifampin – disrupts transcription Table 20-6 Figure 20-1

Antimetabolites Antimetabolites: Sulfonamides and trimethoprim – inhibit folic acid synthesis broad-spectrum effectiveness Figure 20-1

Drug Targets What would be a problem with drugs used to fight fungal infections? How about those used to fight viral infections?

Antibiotic Resistance Mechanisms of resistance: destroy the drug Beta-lactamase - enzyme that destroys penicillins and other beta-lactams alter the drug’s target site increase drug elimination become impermeable to the drug

Antibiotic Resistance Acquisition of resistance: spontaneous mutation transfer of plasmids containing a resistance gene

Antibiotic Resistance Human practices leading to resistance: overuse of antibiotics use of antibiotics by immuno-suppressed individuals Failure of patients to follow a prescribed drug treatment use of antibiotics in animal feed