Loss of Bacterial Cell Pole Stabilization in <named-content content-type="genus-species">Caulobacter crescentus</named-content> Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed Antibiotics

ABSTRACT Rod-shaped bacteria frequently localize proteins to one or both cell poles in order to regulate processes such as chromosome replication or polar organelle development. However, the roles of polar factors in responses to extracellular stimuli have been generally unexplored. We employed chem...

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Autores principales:	Simon-Ulysse Vallet, Lykke Haastrup Hansen, Freja Cecillie Bistrup, Signe Aagaard Laursen, Julien Bortoli Chapalay, Marc Chambon, Gerardo Turcatti, Patrick H. Viollier, Clare L. Kirkpatrick
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	antibiotic resistance Caulobacter crescentus TonB-dependent receptor cell envelope cell polarity vancomycin Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/de7ecdf97d764b25847615ee06483551
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spelling	oai:doaj.org-article:de7ecdf97d764b25847615ee064835512021-11-15T15:56:46ZLoss of Bacterial Cell Pole Stabilization in <named-content content-type="genus-species">Caulobacter crescentus</named-content> Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed Antibiotics10.1128/mBio.00538-202150-7511https://doaj.org/article/de7ecdf97d764b25847615ee064835512020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00538-20https://doaj.org/toc/2150-7511ABSTRACT Rod-shaped bacteria frequently localize proteins to one or both cell poles in order to regulate processes such as chromosome replication or polar organelle development. However, the roles of polar factors in responses to extracellular stimuli have been generally unexplored. We employed chemical-genetic screening to probe the interaction between one such factor from Caulobacter crescentus, TipN, and extracellular stress and found that TipN is required for normal resistance of cell envelope-directed antibiotics, including vancomycin which does not normally inhibit growth of Gram-negative bacteria. Forward genetic screening for suppressors of vancomycin sensitivity in the absence of TipN revealed the TonB-dependent receptor ChvT as the mediator of vancomycin sensitivity. Loss of ChvT improved resistance to vancomycin and cefixime in the otherwise sensitive ΔtipN strain. The activity of the two-component system regulating ChvT (ChvIG) was increased in ΔtipN cells relative to the wild type under some, but not all, cell wall stress conditions that this strain was sensitized to, in particular cefixime and detergent exposure. Together, these results indicate that TipN contributes to cell envelope stress resistance in addition to its roles in intracellular development, and its loss influences signaling through the ChvIG two-component system which has been co-opted as a sensor of cell wall stress in Caulobacter. IMPORTANCE Maintenance of an intact cell envelope is essential for free-living bacteria to protect themselves against their environment. In the case of rod-shaped bacteria, the poles of the cell are potential weak points in the cell envelope due to the high curvature of the layers and the need to break and reform the cell envelope at the division plane as the cells divide. We have found that TipN, a factor required for correct division and cell pole development in Caulobacter crescentus, is also needed for maintaining normal levels of resistance to cell wall-targeting antibiotics such as vancomycin and cefixime, which interfere with peptidoglycan synthesis. Since TipN is normally located at the poles of the cell and at the division plane just before cells complete division, our results suggest that it is involved in stabilization of these weak points of the cell envelope as well as its other roles inside the cell.Simon-Ulysse ValletLykke Haastrup HansenFreja Cecillie BistrupSigne Aagaard LaursenJulien Bortoli ChapalayMarc ChambonGerardo TurcattiPatrick H. ViollierClare L. KirkpatrickAmerican Society for Microbiologyarticleantibiotic resistanceCaulobacter crescentusTonB-dependent receptorcell envelopecell polarityvancomycinMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotic resistance Caulobacter crescentus TonB-dependent receptor cell envelope cell polarity vancomycin Microbiology QR1-502
spellingShingle	antibiotic resistance Caulobacter crescentus TonB-dependent receptor cell envelope cell polarity vancomycin Microbiology QR1-502 Simon-Ulysse Vallet Lykke Haastrup Hansen Freja Cecillie Bistrup Signe Aagaard Laursen Julien Bortoli Chapalay Marc Chambon Gerardo Turcatti Patrick H. Viollier Clare L. Kirkpatrick Loss of Bacterial Cell Pole Stabilization in <named-content content-type="genus-species">Caulobacter crescentus</named-content> Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed Antibiotics
description	ABSTRACT Rod-shaped bacteria frequently localize proteins to one or both cell poles in order to regulate processes such as chromosome replication or polar organelle development. However, the roles of polar factors in responses to extracellular stimuli have been generally unexplored. We employed chemical-genetic screening to probe the interaction between one such factor from Caulobacter crescentus, TipN, and extracellular stress and found that TipN is required for normal resistance of cell envelope-directed antibiotics, including vancomycin which does not normally inhibit growth of Gram-negative bacteria. Forward genetic screening for suppressors of vancomycin sensitivity in the absence of TipN revealed the TonB-dependent receptor ChvT as the mediator of vancomycin sensitivity. Loss of ChvT improved resistance to vancomycin and cefixime in the otherwise sensitive ΔtipN strain. The activity of the two-component system regulating ChvT (ChvIG) was increased in ΔtipN cells relative to the wild type under some, but not all, cell wall stress conditions that this strain was sensitized to, in particular cefixime and detergent exposure. Together, these results indicate that TipN contributes to cell envelope stress resistance in addition to its roles in intracellular development, and its loss influences signaling through the ChvIG two-component system which has been co-opted as a sensor of cell wall stress in Caulobacter. IMPORTANCE Maintenance of an intact cell envelope is essential for free-living bacteria to protect themselves against their environment. In the case of rod-shaped bacteria, the poles of the cell are potential weak points in the cell envelope due to the high curvature of the layers and the need to break and reform the cell envelope at the division plane as the cells divide. We have found that TipN, a factor required for correct division and cell pole development in Caulobacter crescentus, is also needed for maintaining normal levels of resistance to cell wall-targeting antibiotics such as vancomycin and cefixime, which interfere with peptidoglycan synthesis. Since TipN is normally located at the poles of the cell and at the division plane just before cells complete division, our results suggest that it is involved in stabilization of these weak points of the cell envelope as well as its other roles inside the cell.
format	article
author	Simon-Ulysse Vallet Lykke Haastrup Hansen Freja Cecillie Bistrup Signe Aagaard Laursen Julien Bortoli Chapalay Marc Chambon Gerardo Turcatti Patrick H. Viollier Clare L. Kirkpatrick
author_facet	Simon-Ulysse Vallet Lykke Haastrup Hansen Freja Cecillie Bistrup Signe Aagaard Laursen Julien Bortoli Chapalay Marc Chambon Gerardo Turcatti Patrick H. Viollier Clare L. Kirkpatrick
author_sort	Simon-Ulysse Vallet
title	Loss of Bacterial Cell Pole Stabilization in <named-content content-type="genus-species">Caulobacter crescentus</named-content> Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed Antibiotics
title_short	Loss of Bacterial Cell Pole Stabilization in <named-content content-type="genus-species">Caulobacter crescentus</named-content> Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed Antibiotics
title_full	Loss of Bacterial Cell Pole Stabilization in <named-content content-type="genus-species">Caulobacter crescentus</named-content> Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed Antibiotics
title_fullStr	Loss of Bacterial Cell Pole Stabilization in <named-content content-type="genus-species">Caulobacter crescentus</named-content> Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed Antibiotics
title_full_unstemmed	Loss of Bacterial Cell Pole Stabilization in <named-content content-type="genus-species">Caulobacter crescentus</named-content> Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed Antibiotics
title_sort	loss of bacterial cell pole stabilization in <named-content content-type="genus-species">caulobacter crescentus</named-content> sensitizes to outer membrane stress and peptidoglycan-directed antibiotics
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/de7ecdf97d764b25847615ee06483551
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Loss of Bacterial Cell Pole Stabilization in <named-content content-type="genus-species">Caulobacter crescentus</named-content> Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed Antibiotics

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