Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis With Low-Level Linezolid-Resistance

Despite increasing reports of low-level linezolid-resistant enterococci worldwide, the mechanism of this resistance remains poorly understood. Previous transcriptome studies of low-level linezolid-resistant Enterococcus faecalis isolates have demonstrated a number of significantly up-regulated genes...

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Main Authors: Jia Yan, Yun Xia, Mi Yang, Jiaqi Zou, Yingzhu Chen, Dawei Zhang, Liang Ma
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-07-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2018.01698/full
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author Jia Yan
Yun Xia
Mi Yang
Jiaqi Zou
Yingzhu Chen
Dawei Zhang
Liang Ma
author_facet Jia Yan
Yun Xia
Mi Yang
Jiaqi Zou
Yingzhu Chen
Dawei Zhang
Liang Ma
author_sort Jia Yan
collection DOAJ
description Despite increasing reports of low-level linezolid-resistant enterococci worldwide, the mechanism of this resistance remains poorly understood. Previous transcriptome studies of low-level linezolid-resistant Enterococcus faecalis isolates have demonstrated a number of significantly up-regulated genes potentially involved in mediation of drug resistance. However, whether the transcriptome faithfully reflects the proteome remains unknown. In this study, we performed quantitative proteomics analysis of membrane proteins in an E. faecalis isolate (P10748) with low-level linezolid-resistance in comparison with two linezolid-susceptible strains 3138 and ATCC 29212, all of which have been previously investigated by whole transcriptome analysis. A total of 8,197 peptides associated with 1,170 proteins were identified in all three isolates with false discovery rate (FDR) at 1% and P < 0.05. There were 14 significantly up-regulated and 6 significantly down-regulated proteins in strain P10748 compared to strains 3138 and ATCC 29212, which were in general positively correlated with transcription levels revealed in previous transcriptome studies. Our analysis suggests that the low-level linezolid-resistance in E. faecalis is conferred primarily by the ATP-binding cassette protein OptrA through ribosomal protection and, possibly, also by the enterococcal surface protein (Esp) and other proteins through biofilm formation. The genetic transfer of optrA is potentially regulated by the surface exclusion protein Sea1, conjugal transfer protein TraB, replication protein RepA and XRE family transcription regulator protein. This report represents the first investigation of the mechanisms of linezolid-resistance in E. faecalis by a quantitative proteomics approach.
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spelling doaj.art-cc8717e3ebe74f50b383aa97decfd3c42022-12-21T18:47:53ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-07-01910.3389/fmicb.2018.01698380973Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis With Low-Level Linezolid-ResistanceJia Yan0Yun Xia1Mi Yang2Jiaqi Zou3Yingzhu Chen4Dawei Zhang5Liang Ma6Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesDespite increasing reports of low-level linezolid-resistant enterococci worldwide, the mechanism of this resistance remains poorly understood. Previous transcriptome studies of low-level linezolid-resistant Enterococcus faecalis isolates have demonstrated a number of significantly up-regulated genes potentially involved in mediation of drug resistance. However, whether the transcriptome faithfully reflects the proteome remains unknown. In this study, we performed quantitative proteomics analysis of membrane proteins in an E. faecalis isolate (P10748) with low-level linezolid-resistance in comparison with two linezolid-susceptible strains 3138 and ATCC 29212, all of which have been previously investigated by whole transcriptome analysis. A total of 8,197 peptides associated with 1,170 proteins were identified in all three isolates with false discovery rate (FDR) at 1% and P < 0.05. There were 14 significantly up-regulated and 6 significantly down-regulated proteins in strain P10748 compared to strains 3138 and ATCC 29212, which were in general positively correlated with transcription levels revealed in previous transcriptome studies. Our analysis suggests that the low-level linezolid-resistance in E. faecalis is conferred primarily by the ATP-binding cassette protein OptrA through ribosomal protection and, possibly, also by the enterococcal surface protein (Esp) and other proteins through biofilm formation. The genetic transfer of optrA is potentially regulated by the surface exclusion protein Sea1, conjugal transfer protein TraB, replication protein RepA and XRE family transcription regulator protein. This report represents the first investigation of the mechanisms of linezolid-resistance in E. faecalis by a quantitative proteomics approach.https://www.frontiersin.org/article/10.3389/fmicb.2018.01698/fullEnterococcus faecalislinezolidlow-level resistancemembrane proteinsquantitative proteomics
spellingShingle Jia Yan
Yun Xia
Mi Yang
Jiaqi Zou
Yingzhu Chen
Dawei Zhang
Liang Ma
Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis With Low-Level Linezolid-Resistance
Frontiers in Microbiology
Enterococcus faecalis
linezolid
low-level resistance
membrane proteins
quantitative proteomics
title Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis With Low-Level Linezolid-Resistance
title_full Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis With Low-Level Linezolid-Resistance
title_fullStr Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis With Low-Level Linezolid-Resistance
title_full_unstemmed Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis With Low-Level Linezolid-Resistance
title_short Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis With Low-Level Linezolid-Resistance
title_sort quantitative proteomics analysis of membrane proteins in enterococcus faecalis with low level linezolid resistance
topic Enterococcus faecalis
linezolid
low-level resistance
membrane proteins
quantitative proteomics
url https://www.frontiersin.org/article/10.3389/fmicb.2018.01698/full
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