Increased drug permeability of a stiffened mycobacterial outer membrane in cells lacking MFS transporter Rv1410 and lipoprotein LprG

Mol Microbiol. 2019 May;111(5):1263-1282. doi: 10.1111/mmi.14220. Epub 2019 Mar 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Gene Deletion
  • Lactococcus lactis
  • Lipopolysaccharides / pharmacology
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism
  • Microscopy, Atomic Force
  • Microscopy, Electron, Transmission
  • Mutation
  • Mycobacterium abscessus / drug effects
  • Mycobacterium abscessus / genetics
  • Mycobacterium smegmatis / drug effects*
  • Mycobacterium smegmatis / genetics*
  • Mycobacterium smegmatis / ultrastructure
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics
  • Operon*
  • Permeability
  • Protein Structure, Tertiary
  • Rifampin / pharmacology
  • Virulence


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Lipopolysaccharides
  • Membrane Transport Proteins
  • P55 protein, Mycobacterium
  • lipoarabinomannan
  • Rifampin