LIPID-A ACYLATION AND BACTERIAL-RESISTANCE AGAINST VERTEBRATE ANTIMICROBIAL PEPTIDES

The Salmonellae PhoP-PhoQ virulence regulators induce resistance to ho st cationic antimicrobial peptides (CAMP) after infection of vertebrat e tissues, and M2+ or Ca2+ limitation. The PhoP-PhoQ activated gene, p agP, was identified as important to inducible CAMP resistance and incr eased acylation of lipid A, the major component of the outer leaflet o f the outer membrane, pagP mutants demonstrated increased outer membra ne permeability in response to CAMP, supporting the hypothesis that in creased lipid A acylation is a CAMP resistance mechanism. Similarly, i n response to Mg2+ limited growth, other enteric Gramnegative bacteria demonstrated increased lipid A acylation. Compounds that inhibit the ability to increase lipid A acylation may have utility as new antimicr obial agents.