Jones, Rebekah A., Shropshire, Holly, Zhao, Caimeng, Murphy, Andrew, Lidbury, Ian, Wei, Tao, Scanlan, David J. and Chen, Yin (2021) Phosphorus stress induces the synthesis of novel glycolipids in Pseudomonas aeruginosa that confer protection against a last-resort antibiotic. ISME Journal, 15 . pp. 3303-3314. doi:10.1038/s41396-021-01008-7 ISSN 1751-7362.

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Abstract

Pseudomonas aeruginosa is a nosocomial pathogen with a prevalence in immunocompromised individuals and is particularly abundant in the lung microbiome of cystic fibrosis patients. A clinically important adaptation for bacterial pathogens during infection is their ability to survive and proliferate under phosphorus-limited growth conditions. Here, we demonstrate that P. aeruginosa adapts to P-limitation by substituting membrane glycerophospholipids with sugar-containing glycolipids through a lipid renovation pathway involving a phospholipase and two glycosyltransferases. Combining bacterial genetics and multi-omics (proteomics, lipidomics and metatranscriptomic analyses), we show that the surrogate glycolipids monoglucosyldiacylglycerol and glucuronic acid-diacylglycerol are synthesised through the action of a new phospholipase (PA3219) and two glycosyltransferases (PA3218 and PA0842). Comparative genomic analyses revealed that this pathway is strictly conserved in all P. aeruginosa strains isolated from a range of clinical and environmental settings and actively expressed in the metatranscriptome of cystic fibrosis patients. Importantly, this phospholipid-to-glycolipid transition comes with significant ecophysiological consequence in terms of antibiotic sensitivity. Mutants defective in glycolipid synthesis survive poorly when challenged with polymyxin B, a last-resort antibiotic for treating multi-drug resistant P. aeruginosa. Thus, we demonstrate an intriguing link between adaptation to environmental stress (nutrient availability) and antibiotic resistance, mediated through membrane lipid renovation that is an important new facet in our understanding of the ecophysiology of this bacterium in the lung microbiome of cystic fibrosis patients.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RC Internal medicine R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Pseudomonas aeruginosa, Glycolipids, Antibiotics -- Analysis, Cystic fibrosis -- Treatment
Journal or Publication Title:	ISME Journal
Publisher:	Springer Nature
ISSN:	1751-7362
Official Date:	24 May 2021
Dates:	Date Event 24 May 2021 Published 6 May 2021 Accepted
Volume:	15
Page Range:	pp. 3303-3314
DOI:	10.1038/s41396-021-01008-7
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	11 May 2021
Date of first compliant Open Access:	2 June 2021
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID MR/J003964/1 [MRC] Medical Research Council http://dx.doi.org/10.13039/501100000265 IEC\NSFC\170213 ; grant agreement no. 170213 Royal Society http://dx.doi.org/10.13039/501100000288 726116 H2020 European Research Council http://dx.doi.org/10.13039/100010663
Is Part Of:	1
Related URLs:	Publisher

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