Loss of bacterial cell pole stabilization in caulobacter crescentus sensitizes to outer membrane stress and peptidoglycan-directed antibiotics

Article Article scientifique Article Loss of bacterial cell pole stabilization in caulobacter crescentus sensitizes to outer membrane stress and peptidoglycan-directed antibiotics eng 2020 author Vallet Simon 865164 Simon-Ulysse Vallet author Hansen Lykke Haastrup author Bistrup Freja Cecillie author Laursen Signe Aagaard author Chapalay Julien Bortoli author Chambon Marc author Turcatti Gérardo 742415 author Viollier Patrick 0000-0002-5249-9910 706923 author Kirkpatrick Clare 647519 e00538-20 10.1128/mBio.00538-20 32371598 2150-7511 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 CaulobacterIMPORTANCE 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. Dewey 590 Dewey 616 23 Institut de génétique et de génomique 0DH 54 Département de microbiologie et médecine moléculaire 21B false 554 Régulation du cycle cellulaire dans C.crescentus, une bactérie asymétrique 895 mBio 11 3 ce6c4d10-1a6c-4e0f-ba8a-9a2a0cfb5128 Article (Published version) Public mBio-2020-Vallet-e00538-20.full.pdf 2652655 application/pdf CC BY openAccess Centres et instituts / Institut de génétique et de génomique Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

Title	Published in	Year	Views	Downloads

Loss of bacterial cell pole stabilization in caulobacter crescentus sensitizes to outer membrane stress and peptidoglycan-directed antibiotics	mBio	2020	366	159
Growth control switch by a DNA-damage-inducible toxin–antitoxin system in Caulobacter crescentus	Nature microbiology	2016	823	9

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Turcatti, Gérardo