Increased drug permeability of a stiffened mycobacterial outer membrane in cells lacking MFS transporter Rv1410 and lipoprotein LprG.
Anti-Bacterial Agents
/ pharmacology
Bacterial Proteins
/ genetics
Cell Membrane
/ drug effects
Gene Deletion
Lactococcus lactis
Lipopolysaccharides
/ pharmacology
Membrane Transport Proteins
/ genetics
Microscopy, Atomic Force
Microscopy, Electron, Transmission
Mutation
Mycobacterium abscessus
/ drug effects
Mycobacterium smegmatis
/ drug effects
Mycobacterium tuberculosis
/ drug effects
Operon
Permeability
Protein Structure, Tertiary
Rifampin
/ pharmacology
Virulence
Journal
Molecular microbiology
ISSN: 1365-2958
Titre abrégé: Mol Microbiol
Pays: England
ID NLM: 8712028
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
accepted:
06
02
2019
pubmed:
12
2
2019
medline:
31
1
2020
entrez:
12
2
2019
Statut:
ppublish
Résumé
The major facilitator superfamily transporter Rv1410 and the lipoprotein LprG (Rv1411) are encoded by a conserved two-gene operon and contribute to virulence in Mycobacterium tuberculosis. Rv1410 was originally postulated to function as a drug efflux pump, but recent studies suggested that Rv1410 and LprG work in concert to insert triacylglycerides and lipoarabinomannans into the outer membrane. Here, we conducted microscopic analyses of Mycobacterium smegmatis lacking the operon and observed a cell separation defect, while surface rigidity measured by atomic force microscopy was found to be increased. Whereas Rv1410 expressed in Lactococcus lactis did not confer drug resistance, deletion of the operon in Mycobacterium abscessus and M. smegmatis resulted in increased susceptibility toward vancomycin, novobiocin and rifampicin. A homology model of Rv1410 revealed a periplasmic loop as well as a highly conserved aspartate, which were found to be essential for the operon's function. Interestingly, influx of the fluorescent dyes BCECF-AM and calcein-AM in de-energized M. smegmatis cells was faster in the deletion mutant. Our results unambiguously show that elevated drug susceptibility in the deletion mutant is caused by increased drug influx through a defective mycobacterial cell envelope and not by drug efflux mediated by Rv1410.
Identifiants
pubmed: 30742339
doi: 10.1111/mmi.14220
pmc: PMC6519032
doi:
Substances chimiques
Anti-Bacterial Agents
0
Bacterial Proteins
0
Lipopolysaccharides
0
Membrane Transport Proteins
0
P55 protein, Mycobacterium
0
lipoarabinomannan
0
Rifampin
VJT6J7R4TR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1263-1282Informations de copyright
© 2019 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.
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