Listeria intracellular growth and virulence require host-derived lipoic acid.
Listeria monocytogenes is a Gram-positive intracytosolic pathogen that causes severe disease in pregnant and immunocompromised individuals. We found that L. monocytogenes lacking the lipoate protein ligase LplA1 was defective for growth specifically in the host cytosol and was less virulent in animals by a factor of 300. A major target for LplA1, the E2 subunit of pyruvate dehydrogenase (PDH), lacked a critical lipoyl modification when the DeltalplA1 strain was grown intracellularly, which suggests that abortive growth was due to loss of PDH function. Thus, the use of host-derived lipoic acid may be a critical process for in vivo replication of bacterial pathogens.
O'Riordan
Mary
M
Department of Molecular and Cell Biology, School of Public Health, University of California, Berkeley, CA 94720-3202, USA. oriordan@umich.edu
Moors
Marlena A
MA
Portnoy
Daniel A
DA
D000818:Animals; D002460:Cell Line; D003470:Culture Media; D003600:Cytosol / Q000382:microbiology; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D017353:Gene Deletion; D007928:Lethal Dose 50; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D016366:Open Reading Frames; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D008063:Thioctic Acid / Q000378:metabolism*; D014774:Virulence
D003470:Culture Media; D011768:Pyruvate Dehydrogenase Complex; D008063:Thioctic Acid; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D010453:Peptide Synthases; C072322:lipoate-protein ligase