Citation

BibTex format

@article{Gahlot:2024:10.1038/s44259-024-00059-y,
author = {Gahlot, DK and Patkowski, JB and Fernández, de Santaella J and Allsopp, LP and Pan, Z and Filloux, A and Larrouy-Maumus, G and Francis, MS and Costa, TRD},
doi = {10.1038/s44259-024-00059-y},
journal = {npj Antimicrobials and Resistance},
title = {Cpx-signalling in Yersinia pseudotuberculosis modulates Lipid-A remodelling and resistance to last-resort antimicrobials},
url = {http://dx.doi.org/10.1038/s44259-024-00059-y},
volume = {2},
year = {2024}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Antibiotic resistance is a global healthcare crisis. Bacteria are highly adaptable and can rapidly acquire mechanisms of resistance towards conventional antibiotics. The permeability barrier conferred by the Gram-negative bacteria cell envelope constitutes a first line of defence against the action of antibiotics. Exposure to extracytoplasmic stresses can negatively affect cell envelope homoeostasis and this causes localised protein misfolding, compromised envelope integrity and impairs barrier function. The CpxA-CpxR two-component regulatory system has evolved to sense extracytoplasmic stresses and to regulate processes that restore homoeostasis of the cell envelope. Hence, controlled Cpx-signalling assists bacteria in adapting, surviving and proliferating in harsh environments, including exposure to antibiotics. Herein, we determined that an intact Cpx-signalling is key to maintaining the Yersinia pseudotuberculosis resistance to colistin and polymyxin B. The susceptibility displayed by Cpx-signalling defective mutants, correlated with cell-envelope deformity and specific modifications of Lipid-A. In vivo transcriptional analysis and in vitro protein-DNA binding studies demonstrated that these modifications were dependent on the direct regulation of Lipid-A biogenesis and modifications of operons by the active phosphorylated CpxR~P isoform. Altogether, our work defines the regulatory mechanism that enables Cpx-signalling to actively control cell envelope remodelling and the permeability of antibiotics in the clinically relevant enteropathogen Y. pseudotuberculosis.
AU  - Gahlot,DK
AU  - Patkowski,JB
AU  - Fernández,de Santaella J
AU  - Allsopp,LP
AU  - Pan,Z
AU  - Filloux,A
AU  - Larrouy-Maumus,G
AU  - Francis,MS
AU  - Costa,TRD
DO  - 10.1038/s44259-024-00059-y
PY  - 2024///
SN  - 2731-8745
TI  - Cpx-signalling in Yersinia pseudotuberculosis modulates Lipid-A remodelling and resistance to last-resort antimicrobials
T2  - npj Antimicrobials and Resistance
UR  - http://dx.doi.org/10.1038/s44259-024-00059-y
VL  - 2
ER  -
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