Branched-chain fatty acids promote Listeria monocytogenes intracellular infection and virulence.
Anteiso-branched-chain fatty acids (BCFA) represent the dominant group of membrane fatty acids and have been established as crucial determinants in resistance against environmental stresses in Listeria monocytogenes, a facultative intracellular pathogen. Here, we investigate the role of anteiso-BCFA in L. monocytogenes virulence by using mutants deficient in branched-chain alpha-keto acid dehydrogenase (BKD), an enzyme complex involved in the synthesis of BCFA. In tissue culture models of infection, anteiso-BCFA contributed to intracellular growth and survival in macrophages and significantly enhanced plaque formation upon prolonged infection in L2 fibroblasts. The intracellular defects observed could be attributed partially to insufficient listeriolysin O (LLO) production, indicating a requirement for anteiso-BCFA in regulating virulence factor production. In a murine model of infection, the BKD-deficient mutant was highly attenuated, further emphasizing the importance of BKD-mediated metabolism in L. monocytogenes virulence. This study demonstrates an underappreciated role for BCFA in bacterial pathogenesis, which may provide insight into the development and application of antimicrobial agents.
Sun
Yvonne
Y
University of Michigan Medical School, Ann Arbor, MI 48109, USA.
O'Riordan
Mary X D
MX
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003470:Culture Media; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000382:microbiology*; D006801:Humans; D008089:Listeria monocytogenes / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology*; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D014774:Virulence; D037521:Virulence Factors
D003470:Culture Media; D005227:Fatty Acids; D037521:Virulence Factors; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
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