Year: 2021
Type: article
Abstract: 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.
Source: Cell Reports
Authors: Chui-Yoke Chin, Jinshi Zhao, Anna C. Llewellyn, Igor Golovliov, Anders Sjöstedt, Pei Zhou, David S. Weiss
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: G1009331100, G109885369, G1290436481, G1348456262, G1473318974, G2267671145, G2403548153, Delineating immune-subversive mechanisms of Francisella tularensis and utilizing them as therapeutic targets, G280418689, G2960099891, Mechanisms of type VI secretion and its utility as therapeutic target, G3296290207, G3490436785, G3903281911, Biochemistry and Structure of Lipid A Enzymes, G4988431522, G6136261090, G6170114983, G6203352644, G6524500692, G6533422759, G6971164352, G72099500, G7758657173, G7790742854, ArmR: a novel drug target and mediator of antibiotic resistance, G801646709, G8125712521, G8411409486, G8665678873, G9000183464
OpenAlex ID: W3167696980