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Increased drug permeability of a stiffened mycobacterial outer membrane in cells lacking MFS transporter Rv1410 and lipoprotein LprG.
Hohl, Michael; Remm, Sille; Eskandarian, Haig A; Dal Molin, Michael; Arnold, Fabian M; Hürlimann, Lea M; Krügel, Andri; Fantner, Georg E; Sander, Peter; Seeger, Markus A.
Afiliação
  • Hohl M; Institute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
  • Remm S; Institute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
  • Eskandarian HA; Global Health Institute, École polytechnique fédérale de Lausanne, EPFL, Lausanne, Switzerland.
  • Dal Molin M; Institute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
  • Arnold FM; Institute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
  • Hürlimann LM; Institute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
  • Krügel A; Institute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
  • Fantner GE; Interfaculty Institute for Bioengineering, École polytechnique fédérale de Lausanne, EPFL, Lausanne, Switzerland.
  • Sander P; Institute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
  • Seeger MA; National Center for Mycobacteria, Zurich, Switzerland.
Mol Microbiol ; 111(5): 1263-1282, 2019 05.
Article em En | MEDLINE | ID: mdl-30742339
ABSTRACT
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Óperon / Proteínas de Membrana Transportadoras / Proteínas de Bactérias / Mycobacterium smegmatis Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Óperon / Proteínas de Membrana Transportadoras / Proteínas de Bactérias / Mycobacterium smegmatis Idioma: En Ano de publicação: 2019 Tipo de documento: Article