Skip to main content
  • ASM Journals
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Latest Articles
    • COVID-19 Research and News from ASM Journals
    • mSphere of Influence: Commentaries from Early Career Microbiologists
    • Archive
  • Topics
    • Applied and Environmental Science
    • Clinical Science and Epidemiology
    • Ecological and Evolutionary Science
    • Host-Microbe Biology
    • Molecular Biology and Physiology
    • Therapeutics and Prevention
  • For Authors
    • Getting Started
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About mSphere
    • Editor in Chief
    • Board of Editors
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • ASM Journals
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
mSphere
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Latest Articles
    • COVID-19 Research and News from ASM Journals
    • mSphere of Influence: Commentaries from Early Career Microbiologists
    • Archive
  • Topics
    • Applied and Environmental Science
    • Clinical Science and Epidemiology
    • Ecological and Evolutionary Science
    • Host-Microbe Biology
    • Molecular Biology and Physiology
    • Therapeutics and Prevention
  • For Authors
    • Getting Started
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About mSphere
    • Editor in Chief
    • Board of Editors
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
Research Article | Molecular Biology and Physiology

Genomewide Profiling of the Enterococcus faecalis Transcriptional Response to Teixobactin Reveals CroRS as an Essential Regulator of Antimicrobial Tolerance

Rachel L. Darnell, Melanie K. Knottenbelt, Francesca O. Todd Rose, Ian R. Monk, Timothy P. Stinear, Gregory M. Cook
Paul D. Fey, Editor
Rachel L. Darnell
aDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
bMaurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Melanie K. Knottenbelt
aDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Francesca O. Todd Rose
aDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ian R. Monk
cDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timothy P. Stinear
cDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Timothy P. Stinear
Gregory M. Cook
aDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
bMaurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul D. Fey
University of Nebraska Medical Center
Roles: Editor
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/mSphere.00228-19
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

Teixobactin is a new antimicrobial of significant interest. It is active against a number of multidrug-resistant pathogens, including Staphylococcus aureus and Enterococcus faecalis, with no reported mechanisms of teixobactin resistance. However, historically, mechanisms of resistance always exist and arise upon introduction of a new antimicrobial into a clinical setting. Therefore, for teixobactin to remain effective long term, we need to understand how mechanisms of resistance could develop. Here we demonstrate that E. faecalis shows a remarkable intrinsic tolerance to high concentrations of teixobactin. This is of critical importance, as antimicrobial tolerance has been shown to precede the development of antimicrobial resistance. To identify potential pathways responsible for this tolerance, we determined the genomewide expression profile of E. faecalis strain JH2-2 in response to teixobactin using RNA sequencing. A total of 573 genes were differentially expressed (2.0-fold log2 change in expression) in response to teixobactin, with genes involved in cell wall biogenesis and division and transport/binding being among those that were the most upregulated. Comparative analyses of E. faecalis cell wall-targeting antimicrobial transcriptomes identified CroRS, LiaRS, and YclRK to be important two-component regulators of antimicrobial-mediated stress. Further investigation of CroRS demonstrated that deletion of croRS abolished tolerance to teixobactin and to other cell wall-targeting antimicrobials. This highlights the crucial role of CroRS in controlling the molecular response to teixobactin.

IMPORTANCE Teixobactin is a new antimicrobial with no known mechanisms of resistance. Understanding how resistance could develop will be crucial to the success and longevity of teixobactin as a new potent antimicrobial. Antimicrobial tolerance has been shown to facilitate the development of resistance, and we show that E. faecalis is intrinsically tolerant to teixobactin at high concentrations. We subsequently chose E. faecalis as a model to elucidate the molecular mechanism underpinning teixobactin tolerance and how this may contribute to the development of teixobactin resistance.

  • Copyright © 2019 Darnell et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

View Full Text
PreviousNext
Back to top
Download PDF
Citation Tools
Genomewide Profiling of the Enterococcus faecalis Transcriptional Response to Teixobactin Reveals CroRS as an Essential Regulator of Antimicrobial Tolerance
Rachel L. Darnell, Melanie K. Knottenbelt, Francesca O. Todd Rose, Ian R. Monk, Timothy P. Stinear, Gregory M. Cook
mSphere May 2019, 4 (3) e00228-19; DOI: 10.1128/mSphere.00228-19

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print
Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this mSphere article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Genomewide Profiling of the Enterococcus faecalis Transcriptional Response to Teixobactin Reveals CroRS as an Essential Regulator of Antimicrobial Tolerance
(Your Name) has forwarded a page to you from mSphere
(Your Name) thought you would be interested in this article in mSphere.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Genomewide Profiling of the Enterococcus faecalis Transcriptional Response to Teixobactin Reveals CroRS as an Essential Regulator of Antimicrobial Tolerance
Rachel L. Darnell, Melanie K. Knottenbelt, Francesca O. Todd Rose, Ian R. Monk, Timothy P. Stinear, Gregory M. Cook
mSphere May 2019, 4 (3) e00228-19; DOI: 10.1128/mSphere.00228-19
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • INTRODUCTION
    • RESULTS AND DISCUSSION
    • MATERIALS AND METHODS
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

CroRS
Enterococcus
RNA sequencing
teixobactin
antimicrobial resistance
antimicrobial tolerance
mechanisms of resistance

Related Articles

Cited By...

About

  • About mSphere
  • Board of Editors
  • Policies
  • For Reviewers
  • For the Media
  • Embargo Policy
  • For Librarians
  • For Advertisers
  • Alerts
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Author Warranty
  • Types of Articles
  • Getting Started
  • Ethics
  • Contact Us

Follow #mSphereJ

@ASMicrobiology

       

 

Website feedback

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Online ISSN: 2379-5042