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Differential Requirement for PBP1a and PBP1b in In Vivo and In Vitro Fitness of Vibrio cholerae
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
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2014 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 82, no 5, 2115-2124 p.Article in journal (Refereed) Published
Abstract [en]

We investigated the roles of the Vibrio cholerae high-molecular-weight bifunctional penicillin binding proteins, PBP1a and PBP1b, in the fitness of this enteric pathogen. Using a screen for synthetic lethality, we found that the V. cholerae PBP1a and PBP1b proteins, like their Escherichia coli homologues, are each essential in the absence of the other and in the absence of the other's putative activator, the outer membrane lipoproteins LpoA and LpoB, respectively. Comparative analyses of V. cholerae mutants suggest that PBP1a/LpoA of V. cholerae play a more prominent role in generating and/or maintaining the pathogen's cell wall than PBP1b/LpoB.V. cholerae lacking PBP1b or LpoB exhibited wild-type growth under all conditions tested. In contrast, V. cholerae lacking PBP1a or LpoA exhibited growth deficiencies in minimal medium, in the presence of deoxycholate and bile, and in competition assays with wild-type cells both in vitro and in the infant mouse small intestine. PBP1a pathway mutants are particularly impaired in stationary phase, which renders them sensitive to a product(s) present in supernatants from stationary-phase wild-type cells. The marked competitive defect of the PBP1a pathway mutants in vivo was largely absent when exponential-phase cells rather than stationary-phase cells were used to inoculate suckling mice. Thus, at least for V. cholerae PBP1a pathway mutants, the growth phase of the inoculum is a key modulator of infectivity.

Place, publisher, year, edition, pages
2014. Vol. 82, no 5, 2115-2124 p.
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Immunology in the medical area
URN: urn:nbn:se:umu:diva-104178DOI: 10.1128/IAI.00012-14ISI: 000334666200038PubMedID: 24614657OAI: diva2:823567
Available from: 2015-06-18 Created: 2015-06-08 Last updated: 2015-06-18Bibliographically approved

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Cava, Felipe
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Department of Molecular Biology (Faculty of Medicine)Molecular Infection Medicine Sweden (MIMS)
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