Proton Motive Force Disruptors Block Bacterial Competence and Horizontal Gene Transfer.
Animals
Anti-Bacterial Agents
/ adverse effects
Bacterial Proteins
/ antagonists & inhibitors
Drug Resistance, Microbial
/ drug effects
Drug Resistance, Multiple
/ drug effects
Gene Transfer, Horizontal
/ drug effects
Humans
Mice
Proton-Motive Force
Quorum Sensing
/ drug effects
Streptococcus pneumoniae
/ drug effects
Virulence Factors
DNA uptake
Streptococcus pneumoniae
antibiotic resistance
competence development
horizontal gene transfer
transformation
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
08 04 2020
08 04 2020
Historique:
received:
10
12
2019
revised:
14
01
2020
accepted:
03
02
2020
pubmed:
5
3
2020
medline:
30
12
2020
entrez:
5
3
2020
Statut:
ppublish
Résumé
Streptococcus pneumoniae is a commensal of the human nasopharynx that can also cause severe antibiotic-resistant infections. Antibiotics drive the spread of resistance by inducing S. pneumoniae competence, in which bacteria express the transformation machinery that facilitates uptake of exogenous DNA and horizontal gene transfer (HGT). We performed a high-throughput screen and identified potent inhibitors of S. pneumoniae competence, called COM-blockers. COM-blockers limit competence by inhibiting the proton motive force (PMF), thereby disrupting export of a quorum-sensing peptide that regulates the transformation machinery. Known chemical PMF disruptors and alterations in pH homeostasis similarly inhibit competence. COM-blockers limit transformation of clinical multi-drug-resistant strains and HGT in infected mice. At their active concentrations, COM-blockers do not affect growth, compromise antibiotic activity, or elicit detectable resistance. COM-blockers provide an experimental tool to inhibit competence and other PMF-involved processes and could help reduce the spread of virulence factors and antibiotic resistance in bacteria. VIDEO ABSTRACT.
Identifiants
pubmed: 32130952
pii: S1931-3128(20)30073-1
doi: 10.1016/j.chom.2020.02.002
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Bacterial Proteins
0
Virulence Factors
0
competence factor, Streptococcus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
544-555.e3Subventions
Organisme : Swiss National Science Foundation
Pays : Switzerland
Organisme : Swedish Foundation for Strategic Research
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests A.D. and J.-W.V. author the International Patent Application No. PCT/NL2017/050671 WO/2018/070874. Authors declare no other competing interests.