Conformation control of the histidine kinase BceS ofBacillus subtilisby its cognate ABC-transporter facilitates need-based activation of antibiotic resistance

Abstract

AbstractBacteria closely control gene expression to ensure optimal physiological responses to their environment. Such careful gene expression can minimize the fitness cost associated with antibiotic resistance. We previously described a novel regulatory logic in Bacillus subtilis enabling the cell to directly monitor its need for detoxification. This cost‐effective strategy is achieved via a two‐component regulatory system (BceRS) working in a sensory complex with an ABC‐transporter (BceAB), together acting as a flux‐sensor where signaling is proportional to transport activity. How this is realized at the molecular level has remained unknown. Using experimentation and computation we here show that the histidine kinase is activated by piston‐like displacements in the membrane, which are converted to helical rotations in the catalytic core via an intervening HAMP‐like domain. Intriguingly, the transporter was not only required for kinase activation, but also to actively maintain the kinase in its inactive state in the absence of antibiotics. Such coupling of kinase activity to that of the transporter ensures the complete control required for transport flux‐dependent signaling. Moreover, we show that the transporter likely conserves energy by signaling with sub‐maximal sensitivity. These results provide the first mechanistic insights into transport flux‐dependent signaling, a unique strategy for energy‐efficient decision making.

Autoren

Alan Koh
Marjorie J Gibbon
Marc W Van der Kamp
Christopher R Pudney
Susanne Gebhard

DOI

10.1111/mmi.14607

eISSN

1365-2958

ISSN

0950-382X

Ausgabe der Veröffentlichung

1

Zeitschrift

Molecular Microbiology

Sprache

en

Online publication date

2020

Paginierung

157 - 174

Datum der Veröffentlichung

2021

Status

Published

Herausgeber

Wiley

Herausgeber URL

http://dx.doi.org/10.1111/mmi.14607

Datum der Datenerfassung

2023

Titel

Conformation control of the histidine kinase BceS of <i>Bacillus subtilis</i> by its cognate ABC‐transporter facilitates need‐based activation of antibiotic resistance

Ausgabe der Zeitschrift

115

Data source: Crossref

Abstract

Bacteria closely control gene expression to ensure optimal physiological responses to their environment. Such careful gene expression can minimize the fitness cost associated with antibiotic resistance. We previously described a novel regulatory logic in Bacillus subtilis enabling the cell to directly monitor its need for detoxification. This cost-effective strategy is achieved via a two-component regulatory system (BceRS) working in a sensory complex with an ABC-transporter (BceAB), together acting as a flux-sensor where signaling is proportional to transport activity. How this is realized at the molecular level has remained unknown. Using experimentation and computation we here show that the histidine kinase is activated by piston-like displacements in the membrane, which are converted to helical rotations in the catalytic core via an intervening HAMP-like domain. Intriguingly, the transporter was not only required for kinase activation, but also to actively maintain the kinase in its inactive state in the absence of antibiotics. Such coupling of kinase activity to that of the transporter ensures the complete control required for transport flux-dependent signaling. Moreover, we show that the transporter likely conserves energy by signaling with sub-maximal sensitivity. These results provide the first mechanistic insights into transport flux-dependent signaling, a unique strategy for energy-efficient decision making.

Addresses

Department of Biology and Biochemistry, University of Bath, Bath, UK.

Autoren

Alan Koh
Marjorie J Gibbon
Marc W Van der Kamp
Christopher R Pudney
Susanne Gebhard

DOI

10.1111/mmi.14607

eISSN

1365-2958

Externe Identifier

PubMed Identifier: 32955745

Funding acknowledgements

Biotechnology and Biological Sciences Research Council: BB/M026280/1
Biotechnology and Biological Sciences Research Council: BB/M029255/1

Open access

false

ISSN

0950-382X

Ausgabe der Veröffentlichung

1

Zeitschrift

Molecular microbiology

Schlüsselwörter

Bacillus subtilis
Bacitracin
Bacterial Proteins
Membrane Transport Proteins
ATP-Binding Cassette Transporters
Anti-Bacterial Agents
Drug Resistance, Bacterial
Signal Transduction
Gene Expression Regulation, Bacterial
Histidine Kinase

Sprache

eng

Medium

Print-Electronic

Online publication date

2020

Paginierung

157 - 174

Datum der Veröffentlichung

2021

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2020

Titel

Conformation control of the histidine kinase BceS of Bacillus subtilis by its cognate ABC-transporter facilitates need-based activation of antibiotic resistance.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

115

Data source: Europe PubMed Central

Abstract

Bacteria closely control gene expression to ensure optimal physiological responses to their environment. Such careful gene expression can minimize the fitness cost associated with antibiotic resistance. We previously described a novel regulatory logic in Bacillus subtilis enabling the cell to directly monitor its need for detoxification. This cost-effective strategy is achieved via a two-component regulatory system (BceRS) working in a sensory complex with an ABC-transporter (BceAB), together acting as a flux-sensor where signaling is proportional to transport activity. How this is realized at the molecular level has remained unknown. Using experimentation and computation we here show that the histidine kinase is activated by piston-like displacements in the membrane, which are converted to helical rotations in the catalytic core via an intervening HAMP-like domain. Intriguingly, the transporter was not only required for kinase activation, but also to actively maintain the kinase in its inactive state in the absence of antibiotics. Such coupling of kinase activity to that of the transporter ensures the complete control required for transport flux-dependent signaling. Moreover, we show that the transporter likely conserves energy by signaling with sub-maximal sensitivity. These results provide the first mechanistic insights into transport flux-dependent signaling, a unique strategy for energy-efficient decision making.

Date of acceptance

2020

Autoren

Alan Koh
Marjorie J Gibbon
Marc W Van der Kamp
Christopher R Pudney
Susanne Gebhard

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/32955745

DOI

10.1111/mmi.14607

eISSN

1365-2958

Funding acknowledgements

Biotechnology and Biological Sciences Research Council: BB/M026280/1
Biotechnology and Biological Sciences Research Council: BB/M029255/1

Ausgabe der Veröffentlichung

1

Zeitschrift

Mol Microbiol

Schlüsselwörter

antimicrobial peptide
cell envelope stress
flux-sensing
signal transduction
ATP-Binding Cassette Transporters
Anti-Bacterial Agents
Bacillus subtilis
Bacitracin
Bacterial Proteins
Drug Resistance, Bacterial
Gene Expression Regulation, Bacterial
Histidine Kinase
Membrane Transport Proteins
Signal Transduction

Sprache

eng

Country

England

Paginierung

157 - 174

Datum der Veröffentlichung

2021

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2021

Titel

Conformation control of the histidine kinase BceS of Bacillus subtilis by its cognate ABC-transporter facilitates need-based activation of antibiotic resistance.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

115

Data source: PubMed

Conformation control of the histidine kinase BceS ofBacillus subtilisby its cognate ABC-transporter facilitates need-based activation of antibiotic resistance

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