Regulatory interactions between daptomycin- and bacitracin-responsive pathways coordinate the cell envelope antibiotic resistance response of Enterococcus faecalis

Publication type:
Journal article
Metadata:
Autoren
  • Sali M Morris
  • Laura Wiens
  • Olivia Rose
  • Georg Fritz
  • Tim Rogers
  • Susanne Gebhard
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001206477200001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1111/mmi.15264
eISSN
1365-2958
Externe Identifier
  • Clarivate Analytics Document Solution ID: OH8Q4
  • PubMed Identifier: 38646792
ISSN
0950-382X
Zeitschrift
MOLECULAR MICROBIOLOGY
Schlüsselwörter
  • antimicrobial peptides
  • antimicrobial resistance
  • cell envelope stress
  • signalling
  • two-component system
Datum der Veröffentlichung
2024
Status
Published
Titel
Regulatory interactions between daptomycin- and bacitracin-responsive pathways coordinate the cell envelope antibiotic resistance response of <i>Enterococcus faecalis</i>
Sub types
  • Article
  • Early Access

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Abstract</jats:title><jats:p>Enterococcal infections frequently show high levels of antibiotic resistance, including to cell envelope‐acting antibiotics like daptomycin (DAP). While we have a good understanding of the resistance mechanisms, less is known about the control of such resistance genes in enterococci. Previous work unveiled a bacitracin resistance network, comprised of the sensory ABC transporter SapAB, the two‐component system (TCS) SapRS and the resistance ABC transporter RapAB. Interestingly, components of this system have recently been implicated in DAP resistance, a role usually regulated by the TCS LiaFSR. To better understand the regulation of DAP resistance and how this relates to mutations observed in DAP‐resistant clinical isolates of enterococci, we here explored the interplay between these two regulatory pathways. Our results show that SapR regulates an additional resistance operon, <jats:italic>dltXABCD</jats:italic>, a known DAP resistance determinant, and show that LiaFSR regulates the expression of <jats:italic>sapRS</jats:italic>. This regulatory structure places SapRS‐target genes under dual control, where expression is directly controlled by SapRS, which itself is up‐regulated through LiaFSR. The network structure described here shows how <jats:italic>Enterococcus faecalis</jats:italic> coordinates its response to cell envelope attack and can explain why clinical DAP resistance often emerges via mutations in regulatory components.</jats:p>
Autoren
  • Sali M Morris
  • Laura Wiens
  • Olivia Rose
  • Georg Fritz
  • Tim Rogers
  • Susanne Gebhard
DOI
10.1111/mmi.15264
eISSN
1365-2958
ISSN
0950-382X
Zeitschrift
Molecular Microbiology
Sprache
en
Online publication date
2024
Status
Published online
Herausgeber
Wiley
Herausgeber URL
http://dx.doi.org/10.1111/mmi.15264
Datum der Datenerfassung
2024
Titel
Regulatory interactions between daptomycin‐ and bacitracin‐responsive pathways coordinate the cell envelope antibiotic resistance response of <i>Enterococcus faecalis</i>

Data source: Crossref

Abstract
Enterococcal infections frequently show high levels of antibiotic resistance, including to cell envelope-acting antibiotics like daptomycin (DAP). While we have a good understanding of the resistance mechanisms, less is known about the control of such resistance genes in enterococci. Previous work unveiled a bacitracin resistance network, comprised of the sensory ABC transporter SapAB, the two-component system (TCS) SapRS and the resistance ABC transporter RapAB. Interestingly, components of this system have recently been implicated in DAP resistance, a role usually regulated by the TCS LiaFSR. To better understand the regulation of DAP resistance and how this relates to mutations observed in DAP-resistant clinical isolates of enterococci, we here explored the interplay between these two regulatory pathways. Our results show that SapR regulates an additional resistance operon, dltXABCD, a known DAP resistance determinant, and show that LiaFSR regulates the expression of sapRS. This regulatory structure places SapRS-target genes under dual control, where expression is directly controlled by SapRS, which itself is up-regulated through LiaFSR. The network structure described here shows how Enterococcus faecalis coordinates its response to cell envelope attack and can explain why clinical DAP resistance often emerges via mutations in regulatory components.
Addresses
  • Life Sciences Department, Milner Centre for Evolution, University of Bath, Bath, UK.
Autoren
  • Sali M Morris
  • Laura Wiens
  • Olivia Rose
  • Georg Fritz
  • Tim Rogers
  • Susanne Gebhard
DOI
10.1111/mmi.15264
eISSN
1365-2958
Externe Identifier
  • PubMed Identifier: 38646792
Funding acknowledgements
  • Medical Research Council: MR/N0137941/1
Open access
false
ISSN
0950-382X
Zeitschrift
Molecular microbiology
Sprache
eng
Medium
Print-Electronic
Online publication date
2024
Datum der Veröffentlichung
2024
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2024
Titel
Regulatory interactions between daptomycin- and bacitracin-responsive pathways coordinate the cell envelope antibiotic resistance response of Enterococcus faecalis.
Sub types
  • Journal Article

Data source: Europe PubMed Central

Abstract
Enterococcal infections frequently show high levels of antibiotic resistance, including to cell envelope-acting antibiotics like daptomycin (DAP). While we have a good understanding of the resistance mechanisms, less is known about the control of such resistance genes in enterococci. Previous work unveiled a bacitracin resistance network, comprised of the sensory ABC transporter SapAB, the two-component system (TCS) SapRS and the resistance ABC transporter RapAB. Interestingly, components of this system have recently been implicated in DAP resistance, a role usually regulated by the TCS LiaFSR. To better understand the regulation of DAP resistance and how this relates to mutations observed in DAP-resistant clinical isolates of enterococci, we here explored the interplay between these two regulatory pathways. Our results show that SapR regulates an additional resistance operon, dltXABCD, a known DAP resistance determinant, and show that LiaFSR regulates the expression of sapRS. This regulatory structure places SapRS-target genes under dual control, where expression is directly controlled by SapRS, which itself is up-regulated through LiaFSR. The network structure described here shows how Enterococcus faecalis coordinates its response to cell envelope attack and can explain why clinical DAP resistance often emerges via mutations in regulatory components.
Date of acceptance
2024
Autoren
  • Sali M Morris
  • Laura Wiens
  • Olivia Rose
  • Georg Fritz
  • Tim Rogers
  • Susanne Gebhard
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/38646792
DOI
10.1111/mmi.15264
eISSN
1365-2958
Funding acknowledgements
  • Medical Research Council: MR/N0137941/1
Zeitschrift
Mol Microbiol
Schlüsselwörter
  • antimicrobial peptides
  • antimicrobial resistance
  • cell envelope stress
  • signalling
  • two‐component system
Sprache
eng
Country
England
Datum der Veröffentlichung
2024
Status
Published online
Titel
Regulatory interactions between daptomycin- and bacitracin-responsive pathways coordinate the cell envelope antibiotic resistance response of Enterococcus faecalis.
Sub types
  • Journal Article

Data source: PubMed

Author's licence
CC-BY
Autoren
  • Sali M Morris
  • Laura Wiens
  • Olivia Rose
  • Georg Fritz
  • Tim Rogers
  • Susanne Gebhard
Hosting institution
Universitätsbibliothek Mainz
Resource version
Published version
DOI
10.1111/mmi.15264
File(s) embargoed
false
Open access
true
ISSN
0950-382X
Zeitschrift
Molecular microbiology
Sprache
eng
Open access status
Open Access
Herausgeber
Wiley-Blackwell
Zugang
Private
Titel
Regulatory interactions between daptomycin- and bacitracin-responsive pathways coordinate the cell envelope antibiotic resistance response of Enterococcus faecalis
Ausgabe der Zeitschrift
2024

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regulatory_interactions_betwe-20240522114445527.pdf

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