umu.sePublications
Change search
ReferencesLink to record
Permanent link

Direct link
A cell wall damage response mediated by a sensor kinase/response regulator pair enables beta-lactam tolerance
Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Show others and affiliations
2016 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 2, 404-409 p.Article in journal (Refereed) PublishedText
Abstract [en]

The bacterial cell wall is critical for maintenance of cell shape and survival. Following exposure to antibiotics that target enzymes required for cell wall synthesis, bacteria typically lyse. Although several cell envelope stress response systems have been well described, there is little knowledge of systems that modulate cell wall synthesis in response to cell wall damage, particularly in Gram-negative bacteria. Here we describe WigK/WigR, a histidine kinase/response regulator pair that enables Vibrio cholerae, the cholera pathogen, to survive exposure to antibiotics targeting cell wall synthesis in vitro and during infection. Unlike wild-type V. cholerae, mutants lacking wigR fail to recover following exposure to cell-wall-acting antibiotics, and they exhibit a drastically increased cell diameter in the absence of such antibiotics. Conversely, overexpression of wigR leads to cell slimming. Overexpression of activated WigR also results in increased expression of the full set of cell wall synthesis genes and to elevated cell wall content. WigKR-dependent expression of cell wall synthesis genes is induced by various cell-wall-acting antibiotics as well as by overexpression of an endogenous cell wall hydrolase. Thus, WigKR appears to monitor cell wall integrity and to enhance the capacity for increased cell wall production in response to damage. Taken together, these findings implicate WigKR as a regulator of cell wall synthesis that controls cell wall homeostasis in response to antibiotics and likely during normal growth as well.

Place, publisher, year, edition, pages
2016. Vol. 113, no 2, 404-409 p.
Keyword [en]
peptidoglycan, stress response, antibiotic tolerance, two component system, cell envelope
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-114884DOI: 10.1073/pnas.1520333113ISI: 000367881500053PubMedID: 26712007OAI: oai:DiVA.org:umu-114884DiVA: diva2:923804
Funder
Knut and Alice Wallenberg FoundationSwedish Research CouncilThe Kempe Foundations
Available from: 2016-04-27 Created: 2016-01-29 Last updated: 2016-04-27Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Alvarez, LauraCava, Felipe
By organisation
Umeå Centre for Microbial Research (UCMR)Department of Molecular Biology (Faculty of Medicine)Molecular Infection Medicine Sweden (MIMS)
In the same journal
Proceedings of the National Academy of Sciences of the United States of America
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 47 hits
ReferencesLink to record
Permanent link

Direct link