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Infection and Immunity, June 2004, p. 3577-3583, Vol. 72, No. 6
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.6.3577-3583.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
The Vibrio cholerae ToxR-Regulated Porin OmpU Confers Resistance to Antimicrobial Peptides
Jyoti Mathur and Matthew K. Waldor*
Department of Immunology, Sackler School of Biomedical Sciences, Tufts University School of Medicine and Howard Hughes Medical Institute, Boston, Massachusetts 02111
Received 3 November 2003/
Returned for modification 30 December 2003/
Accepted 11 February 2004
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.
* Corresponding author. Mailing address: Departments of Immunology and Microbiology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Phone: (617) 636-2730. Fax: (617) 636-2723. E-mail:
matthew.waldor{at}tufts.edu.
Editor: V. J. DiRita
Infection and Immunity, June 2004, p. 3577-3583, Vol. 72, No. 6
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.6.3577-3583.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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