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Francisella FlmX broadly affects lipopolysaccharide modification and virulence.

Publication ,  Journal Article
Chin, C-Y; Zhao, J; Llewellyn, AC; Golovliov, I; Sjöstedt, A; Zhou, P; Weiss, DS
Published in: Cell Rep
June 15, 2021

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.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

June 15, 2021

Volume

35

Issue

11

Start / End Page

109247

Location

United States

Related Subject Headings

  • Virulence
  • Polymyxin B
  • O Antigens
  • Models, Biological
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Lipopolysaccharides
  • Immunity, Innate
  • Gene Expression Regulation, Bacterial
 

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Chin, C.-Y., Zhao, J., Llewellyn, A. C., Golovliov, I., Sjöstedt, A., Zhou, P., & Weiss, D. S. (2021). Francisella FlmX broadly affects lipopolysaccharide modification and virulence. Cell Rep, 35(11), 109247. https://doi.org/10.1016/j.celrep.2021.109247
Chin, Chui-Yoke, Jinshi Zhao, Anna C. Llewellyn, Igor Golovliov, Anders Sjöstedt, Pei Zhou, and David S. Weiss. “Francisella FlmX broadly affects lipopolysaccharide modification and virulence.Cell Rep 35, no. 11 (June 15, 2021): 109247. https://doi.org/10.1016/j.celrep.2021.109247.
Chin C-Y, Zhao J, Llewellyn AC, Golovliov I, Sjöstedt A, Zhou P, et al. Francisella FlmX broadly affects lipopolysaccharide modification and virulence. Cell Rep. 2021 Jun 15;35(11):109247.
Chin, Chui-Yoke, et al. “Francisella FlmX broadly affects lipopolysaccharide modification and virulence.Cell Rep, vol. 35, no. 11, June 2021, p. 109247. Pubmed, doi:10.1016/j.celrep.2021.109247.
Chin C-Y, Zhao J, Llewellyn AC, Golovliov I, Sjöstedt A, Zhou P, Weiss DS. Francisella FlmX broadly affects lipopolysaccharide modification and virulence. Cell Rep. 2021 Jun 15;35(11):109247.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

June 15, 2021

Volume

35

Issue

11

Start / End Page

109247

Location

United States

Related Subject Headings

  • Virulence
  • Polymyxin B
  • O Antigens
  • Models, Biological
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Lipopolysaccharides
  • Immunity, Innate
  • Gene Expression Regulation, Bacterial