Francisella FlmX broadly affects lipopolysaccharide modification and virulence

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Chin, Chui-YokeEmory Antibiotic Resistance Center, Emory University School of Medicine, GA, Atlanta, United States; Emory Vaccine Center, Emory University School of Medicine, GA, Atlanta, United States; Yerkes National Primate Research Center, Emory University School of Medicine, GA, Atlanta, United States; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, GA, Atlanta, United States (author)

Francisella FlmX broadly affects lipopolysaccharide modification and virulence

Article/chapterEnglish2021

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Elsevier,2021
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LIBRIS-ID:oai:DiVA.org:umu-186362
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-186362URI
https://doi.org/10.1016/j.celrep.2021.109247DOI

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Language:English
Summary in:English

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Mikrobiologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Microbiology in the medical area hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi Medicinsk bioteknologi hsv//swe
MEDICAL AND HEALTH SCIENCES Medical Biotechnology Medical Biotechnology hsv//eng
cationic antimicrobial peptide
flippase
lipid A
lipopolysaccharide
polymyxin resistance

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Zhao, JinshiDepartment of Biochemistry, Duke University School of Medicine, NC, Durham, United States (author)
Llewellyn, Anna C.Emory Vaccine Center, Emory University School of Medicine, GA, Atlanta, United States; Yerkes National Primate Research Center, Emory University School of Medicine, GA, Atlanta, United States; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, GA, Atlanta, United States (author)
Golovliov, Igor,1958-Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Klinisk bakteriologi(Swepub:umu)igrgov98 (author)
Sjöstedt, AndersUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Klinisk bakteriologi(Swepub:umu)ansj0004 (author)
Zhou, PeiDepartment of Biochemistry, Duke University School of Medicine, NC, Durham, United States (author)
Weiss, David S.Emory Antibiotic Resistance Center, Emory University School of Medicine, GA, Atlanta, United States; Emory Vaccine Center, Emory University School of Medicine, GA, Atlanta, United States; Yerkes National Primate Research Center, Emory University School of Medicine, GA, Atlanta, United States; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, GA, Atlanta, United States; Research Service, Atlanta VA Medical Center, GA, Decatur, United States (author)
Emory Antibiotic Resistance Center, Emory University School of Medicine, GA, Atlanta, United States; Emory Vaccine Center, Emory University School of Medicine, GA, Atlanta, United States; Yerkes National Primate Research Center, Emory University School of Medicine, GA, Atlanta, United States; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, GA, Atlanta, United StatesDepartment of Biochemistry, Duke University School of Medicine, NC, Durham, United States (creator_code:org_t)

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In:Cell Reports: Elsevier35:112211-1247

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