Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.

<h4>Background</h4>The lipopeptide antibiotic, daptomycin (DAP) interacts with the bacterial cell membrane (CM). Development of DAP resistance during therapy in a clinical strain of Enterococcus faecalis was associated with mutations in genes encoding enzymes involved in cell envelope ho...

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Autores principales:	Nagendra N Mishra, Arnold S Bayer, Truc T Tran, Yousif Shamoo, Eugenia Mileykovskaya, William Dowhan, Ziqiang Guan, Cesar A Arias
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1c28beb628d446718a33d82684844bc9
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spelling	oai:doaj.org-article:1c28beb628d446718a33d82684844bc92021-11-18T07:07:30ZDaptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.1932-620310.1371/journal.pone.0043958https://doaj.org/article/1c28beb628d446718a33d82684844bc92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22952824/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The lipopeptide antibiotic, daptomycin (DAP) interacts with the bacterial cell membrane (CM). Development of DAP resistance during therapy in a clinical strain of Enterococcus faecalis was associated with mutations in genes encoding enzymes involved in cell envelope homeostasis and phospholipid metabolism. Here we characterized changes in CM phospholipid profiles associated with development of DAP resistance in clinical enterococcal strains.<h4>Methodology</h4>Using two clinical strain-pairs of DAP-susceptible and DAP-resistant E. faecalis (S613 vs. R712) and E. faecium (S447 vs. R446) recovered before and after DAP therapy, we compared four distinct CM profiles: phospholipid content, fatty acid composition, membrane fluidity and capacity to be permeabilized and/or depolarized by DAP. Additionally, we characterized the cell envelope of the E. faecium strain-pair by transmission electron microscopy and determined the relative cell surface charge of both strain-pairs.<h4>Principal findings</h4>Both E. faecalis and E. faecium mainly contained four major CM PLs: phosphatidylglycerol (PG), cardiolipin, lysyl-phosphatidylglycerol (L-PG) and glycerolphospho-diglycodiacylglycerol (GP-DGDAG). In addition, E. faecalis CMs (but not E. faecium) also contained: i) phosphatidic acid; and ii) two other unknown species of amino-containing PLs. Development of DAP resistance in both enterococcal species was associated with a significant decrease in CM fluidity and PG content, with a concomitant increase in GP-DGDAG. The strain-pairs did not differ in their outer CM translocation (flipping) of amino-containing PLs. Fatty acid content did not change in the E. faecalis strain-pair, whereas a significant decrease in unsaturated fatty acids was observed in the DAP-resistant E. faecium isolate R446 (vs S447). Resistance to DAP in E. faecium was associated with distinct structural alterations of the cell envelope and cell wall thickening, as well as a decreased ability of DAP to depolarize and permeabilize the CM.<h4>Conclusion</h4>Distinct alterations in PL content and fatty acid composition are associated with development of enterococcal DAP resistance.Nagendra N MishraArnold S BayerTruc T TranYousif ShamooEugenia MileykovskayaWilliam DowhanZiqiang GuanCesar A AriasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e43958 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nagendra N Mishra Arnold S Bayer Truc T Tran Yousif Shamoo Eugenia Mileykovskaya William Dowhan Ziqiang Guan Cesar A Arias Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.
description	<h4>Background</h4>The lipopeptide antibiotic, daptomycin (DAP) interacts with the bacterial cell membrane (CM). Development of DAP resistance during therapy in a clinical strain of Enterococcus faecalis was associated with mutations in genes encoding enzymes involved in cell envelope homeostasis and phospholipid metabolism. Here we characterized changes in CM phospholipid profiles associated with development of DAP resistance in clinical enterococcal strains.<h4>Methodology</h4>Using two clinical strain-pairs of DAP-susceptible and DAP-resistant E. faecalis (S613 vs. R712) and E. faecium (S447 vs. R446) recovered before and after DAP therapy, we compared four distinct CM profiles: phospholipid content, fatty acid composition, membrane fluidity and capacity to be permeabilized and/or depolarized by DAP. Additionally, we characterized the cell envelope of the E. faecium strain-pair by transmission electron microscopy and determined the relative cell surface charge of both strain-pairs.<h4>Principal findings</h4>Both E. faecalis and E. faecium mainly contained four major CM PLs: phosphatidylglycerol (PG), cardiolipin, lysyl-phosphatidylglycerol (L-PG) and glycerolphospho-diglycodiacylglycerol (GP-DGDAG). In addition, E. faecalis CMs (but not E. faecium) also contained: i) phosphatidic acid; and ii) two other unknown species of amino-containing PLs. Development of DAP resistance in both enterococcal species was associated with a significant decrease in CM fluidity and PG content, with a concomitant increase in GP-DGDAG. The strain-pairs did not differ in their outer CM translocation (flipping) of amino-containing PLs. Fatty acid content did not change in the E. faecalis strain-pair, whereas a significant decrease in unsaturated fatty acids was observed in the DAP-resistant E. faecium isolate R446 (vs S447). Resistance to DAP in E. faecium was associated with distinct structural alterations of the cell envelope and cell wall thickening, as well as a decreased ability of DAP to depolarize and permeabilize the CM.<h4>Conclusion</h4>Distinct alterations in PL content and fatty acid composition are associated with development of enterococcal DAP resistance.
format	article
author	Nagendra N Mishra Arnold S Bayer Truc T Tran Yousif Shamoo Eugenia Mileykovskaya William Dowhan Ziqiang Guan Cesar A Arias
author_facet	Nagendra N Mishra Arnold S Bayer Truc T Tran Yousif Shamoo Eugenia Mileykovskaya William Dowhan Ziqiang Guan Cesar A Arias
author_sort	Nagendra N Mishra
title	Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.
title_short	Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.
title_full	Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.
title_fullStr	Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.
title_full_unstemmed	Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.
title_sort	daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1c28beb628d446718a33d82684844bc9
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Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content.

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