PMID:15155667

Citation	Mathur, J and Waldor, MK (2004) The Vibrio cholerae ToxR-regulated porin OmpU confers resistance to antimicrobial peptides. Infect. Immun. 72:3577-83
Abstract	BPI (bactericidal/permeability-increasing) is a potent antimicrobial protein that was recently reported to be expressed as a surface protein on human gastrointestinal tract epithelial cells. In this study, we investigated the resistance of Vibrio cholerae, a small-bowel pathogen that causes cholera, to a BPI-derived peptide, P2. Unlike in Escherichia coli and Salmonella enterica serovar Typhimurium, resistance to P2 in V. cholerae was not dependent on the BipA GTPase. Instead, we found that ToxR, the master regulator of V. cholerae pathogenicity, controlled resistance to P2 by regulating the production of the outer membrane protein OmpU. Both toxR and ompU mutants were at least 100-fold more sensitive to P2 than were wild-type cells. OmpU also conferred resistance to polymyxin B sulfate, suggesting that this porin may impart resistance to cationic antibacterial proteins via a common mechanism. Studies of stationary-phase cells revealed that the ToxR-repressed porin OmpT may also contribute to P2 resistance. Finally, although the mechanism of porin-mediated resistance to antimicrobial peptides remains elusive, our data suggest that the BPI peptide sensitivity of OmpU-deficient V. cholerae is not attributable to a generally defective outer membrane.
Links	PubMed PMC415678 Online version:10.1128/IAI.72.6.3577-3583.2004
Keywords	Adhesins, Bacterial/genetics; Adhesins, Bacterial/metabolism; Amino Acid Sequence; Anti-Infective Agents/pharmacology; Antimicrobial Cationic Peptides; Bacterial Outer Membrane Proteins/genetics; Bacterial Outer Membrane Proteins/metabolism; Bacterial Proteins/metabolism; Blood Proteins/chemistry; Blood Proteins/pharmacology; Cell Membrane Permeability/drug effects; DNA-Binding Proteins/metabolism; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Membrane Proteins; Microbial Sensitivity Tests; Molecular Sequence Data; Peptides/chemical synthesis; Peptides/chemistry; Peptides/pharmacology; Transcription Factors/metabolism; Vibrio cholerae/drug effects; Vibrio cholerae/growth & development; Vibrio cholerae/pathogenicity
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
VIBCH:OMPU		GO:0030153: bacteriocin immunity	ECO:0000315:		P		Fig. 3; shows percent survival of mid-log-phase wild type and ompU mutant when exposed to P2. Western blot analysis was used to show OmpU expression.	complete CACAO 4444

References

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