title: Lipoprotein biosynthesis by prolipoprotein diacylglyceryl transferase is required for efficient spore germination and full virulence of Bacillus anthracis.
abstract: Bacterial lipoproteins play a crucial role in virulence in some gram-positive bacteria. However, the role of lipoprotein biosynthesis in Bacillus anthracis is unknown. We created a B. anthracis mutant strain altered in lipoproteins by deleting the lgt gene encoding the enzyme prolipoprotein diacylglyceryl transferase, which attaches the lipid anchor to prolipoproteins. (14)C-palmitate labelling confirmed that the mutant strain lacked lipoproteins, and hydrocarbon partitioning showed it to have decreased surface hydrophobicity. The anthrax toxin proteins were secreted from the mutant strain at nearly the same levels as from the wild-type strain. The TLR2-dependent TNF-α response of macrophages to heat-killed lgt mutant bacteria was reduced. Spores of the lgt mutant germinated inefficiently in vitro and in mouse skin. As a result, in a murine subcutaneous infection model, lgt mutant spores had markedly attenuated virulence. In contrast, vegetative cells of the lgt mutant were as virulent as those of the wild-type strain. Thus, lipoprotein biosynthesis in B. anthracis is required for full virulence in a murine infection model.
authors: Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Shu
authors: S
authors: Okugawa
authors: Mahtab
authors: M
authors: Moayeri
authors: Andrei P
authors: AP
authors: Pomerantsev
authors: Inka
authors: I
authors: Sastalla
authors: Devorah
authors: D
authors: Crown
authors: Pradeep K
authors: PK
authors: Gupta
authors: Stephen H
authors: SH
authors: Leppla
mesh_terms: D000818:Animals; D000881:Anthrax / Q000382:microbiology*; D001408:Bacillus anthracis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D011498:Protein Precursors / Q000096:biosynthesis*; D013171:Spores, Bacterial / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D014166:Transferases / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D008074:Lipoproteins; D011498:Protein Precursors; D014166:Transferases; C042308:phosphatidylglycerol glyceryl transferase