Biochemical and physiologic basis for susceptibility and resistance of Pseudomonas aeruginosa to antimicrobial agents.
The mechanisms involved in the susceptibility and resistance of Pseudomonas aeruginosa to antimicrobial agents are varied. For the beta-lactam agents, susceptibility of the organism is dependent on penetration of the outer membrane, binding to target proteins, absence of significant beta-lactamases, and, possibly, the initiation of cell wall lysis. Susceptibility to aminoglycosides is based on membrane permeation and transport and specific binding to the 30S ribosomal subunit. Antipseudomonal activity of the polymyxins is related to their binding to membrane phospholipids, with subsequent disruption of the membrane; and activity of tetracycline and erythromycin, which is pH-dependent, affects protein synthesis. Resistance to beta-lactam agents is mediated through beta-lactamases, the Id and V enzymes being especially important in P. aeruginosa. Other postulated mechanisms of resistance include the presence of a permeability barrier, insensitivity of target sites, decreased binding, and "trapping." Decreased binding to the S12 protein (often termed the P10 protein in references to streptomycin), decreased active transport, and enzyme-mediated modification are the major mechanisms responsible for resistance to aminoglycosides. The factors involved in resistance to tetracycline and erythromycin remain unclear. The emergence of resistance during a single course of beta-lactam therapy is a special problem with P. aeruginosa and may be due to acquisition of resistance genes, cross-infection, selection or induction of resistance in some variants, or mutation.
D000617:Aminoglycosides / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D006801:Humans; D007769:Lactams; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D007769:Lactams