title: The BB0646 protein demonstrates lipase and haemolytic activity associated with Borrelia burgdorferi, the aetiological agent of Lyme disease.
abstract: The etiological agent of Lyme disease, Borrelia burgdorferi, is transmitted by ticks of the Ixodes genus and, if untreated, can cause significant morbidity in affected individuals. Recent reports have shown that polyunsaturated fatty acids in the B. burgdorferi cell envelope are potential targets for oxidative damage, which can be lethal. How B. burgdorferi responds to this assault is not known. Herein we report evidence that bb0646 codes for a lipase that is located within the bosR operon and that has specificity for both saturated and polyunsaturated fatty acids. Specifically, strains harbouring mutated copies of the lipase, either in the form of an insertionally inactivated construct or site-directed mutations within the active site, demonstrated attenuated lipolytic and haemolytic phenotypes when compared with the isogenic parent and trans-complements. In vivo analysis showed that while the bb0646 mutant remains infectious, the spirochaetal load is significantly lower than both the isogenic parent and the complemented mutant strains. Taken together, these data demonstrate that BB0646 is a broad substrate specific lipase that contributes to lipolytic and haemolytic activity in vitro and is required for optimal B. burgdorferi infection.
authors.affiliation: Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M Health Science Center, Bryan, Texas 77807, USA.
authors.forename: Dana K
authors.initials: DK
authors.lastname: Shaw
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Hyde
authors.forename: Jon T
authors.initials: JT
authors.lastname: Skare
mesh_terms: D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D058491:Bacterial Load; D025065:Borrelia burgdorferi / Q000201:enzymology* / Q000235:genetics; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008193:Lyme Disease / Q000382:microbiology / Q000473:pathology; D051379:Mice; D016254:Mutagenesis, Insertional; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D009876:Operon
chemical_list: D005227:Fatty Acids; D006460:Hemolysin Proteins; D008049:Lipase