title: Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides.
abstract: The Salmonellae PhoP-PhoQ virulence regulators induce resistance to host cationic antimicrobial peptides (CAMP) after infection of vertebrate tissues, and Mg2+ or Ca2+ limitation. The PhoP-PhoQ activated gene, pagP, was identified as important to inducible CAMP resistance and increased acylation of lipid A, the major component of the outer leaflet of the outer membrane. pagP mutants demonstrated increased outer membrane permeability in response to CAMP, supporting the hypothesis that increased lipid A acylation is a CAMP resistance mechanism. Similarly, in response to Mg2+ limited growth, other enteric Gram-negative bacteria demonstrated increased lipid A acylation. Compounds that inhibit the ability to increase lipid A acylation may have utility as new antimicrobial agents.
authors.affiliation: Department of Microbiology, University of Washington, Seattle 98195, USA.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.forename: K B
authors.initials: KB
authors.lastname: Lim
authors.forename: C M
authors.initials: CM
authors.lastname: Poduje
authors.forename: M
authors.initials: M
authors.lastname: Daniel
authors.forename: J S
authors.initials: JS
authors.lastname: Gunn
authors.forename: M
authors.initials: M
authors.lastname: Hackett
authors.forename: S I
authors.initials: SI
authors.lastname: Miller
mesh_terms: D000215:Acylation; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics; D002412:Cations / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002876:Chromosomes, Bacterial; D003470:Culture Media; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000737:chemistry / Q000254:growth & development; D008050:Lipid A / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008969:Molecular Sequence Data; D010168:Palmitates / Q000378:metabolism; D010455:Peptides; D012486:Salmonella typhimurium / Q000737:chemistry / Q000378:metabolism / Q000472:pathogenicity*; D014157:Transcription Factors / Q000235:genetics; D014774:Virulence; D015008:Yersinia enterocolitica / Q000737:chemistry / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002412:Cations; D003470:Culture Media; D008050:Lipid A; D010168:Palmitates; D010455:Peptides; C079792:PhoQ protein, Bacteria; D014157:Transcription Factors; C061064:PhoP protein, Bacteria; D008274:Magnesium