Antimicrobial peptide resistance mechanisms of human bacterial pathogens.
The critical role played by antimicrobial peptides (AMPs) in mammalian innate immunity is increasingly recognized. Bacteria differ in their intrinsic susceptibility to AMPs, and the relative resistance of some important human pathogens to these defense molecules is now appreciated as an important virulence phenotype. Experimental analysis has identified diverse mechanisms of bacterial AMP resistance including altered cell surface charge, active efflux, production of proteases or trapping proteins, and modification of host cellular processes. The contribution of these resistance mechanisms to pathogenesis is confirmed through direct comparison of wild-type bacteria and AMP-sensitive mutants using in vivo infection models. Knowledge of the molecular basis of bacterial AMP resistance may provide new targets for antimicrobial therapy of human infectious diseases.
Nizet
Victor
V
Department of Pediatrics, Division of Infectious Diseases, University of California, San Diego, 9500 Gilman Drive, MC 0687, La Jolla, CA 92093-0687, USA. vnizet@ucsd.edu
D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000472:pathogenicity*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009894:Opportunistic Infections; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding; D014774:Virulence / Q000235:genetics
D000900:Anti-Bacterial Agents; D010455:Peptides; D000249:Adenosine Monophosphate