Francisella FlmX broadly affects lipopolysaccharide modification and virulence.

Journal Article (Journal Article)

The outer membrane protects Gram-negative bacteria from the host environment. Lipopolysaccharide (LPS), a major outer membrane constituent, has distinct components (lipid A, core, O-antigen) generated by specialized pathways. In this study, we describe the surprising convergence of these pathways through FlmX, an uncharacterized protein in the intracellular pathogen Francisella. FlmX is in the flippase family, which includes proteins that traffic lipid-linked envelope components across membranes. flmX deficiency causes defects in lipid A modification, core remodeling, and O-antigen addition. We find that an F. tularensis mutant lacking flmX is >1,000,000-fold attenuated. Furthermore, FlmX is required to resist the innate antimicrobial LL-37 and the antibiotic polymyxin. Given FlmX's central role in LPS modification and its conservation in intracellular pathogens Brucella, Coxiella, and Legionella, FlmX may represent a novel drug target whose inhibition could cripple bacterial virulence and sensitize bacteria to innate antimicrobials and antibiotics.

Full Text

Duke Authors

Cited Authors

  • Chin, C-Y; Zhao, J; Llewellyn, AC; Golovliov, I; Sjöstedt, A; Zhou, P; Weiss, DS

Published Date

  • June 15, 2021

Published In

Volume / Issue

  • 35 / 11

Start / End Page

  • 109247 -

PubMed ID

  • 34133919

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2021.109247


  • eng

Conference Location

  • United States