title: BB0744 Affects Tissue Tropism and Spatial Distribution of Borrelia burgdorferi.
abstract: Borrelia burgdorferi, the etiologic agent of Lyme disease, produces a variety of proteins that promote survival and colonization in both the Ixodes species vector and various mammalian hosts. We initially identified BB0744 (also known as p83/100) by screening for B. burgdorferi strain B31 proteins that bind to α1β1 integrin and hypothesized that, given the presence of a signal peptide, BB0744 may be a surface-exposed protein. In contrast to this expectation, localization studies suggested that BB0744 resides in the periplasm. Despite its subsurface location, we were interested in testing whether BB0744 is required for borrelial pathogenesis. To this end, a bb0744 deletion was isolated in a B. burgdorferi strain B31 infectious background, complemented, and queried for the role of BB0744 following experimental infection. A combination of bioluminescent imaging, cultivation of infected tissues, and quantitative PCR (qPCR) demonstrated that Δbb0744 mutant B. burgdorferi bacteria were attenuated in the ability to colonize heart tissue, as well as skin locations distal to the site of infection. Furthermore, qPCR indicated a significantly reduced spirochetal load in distal skin and joint tissue infected with Δbb0744 mutant B. burgdorferi. Complementation with bb0744 restored infectivity, indicating that the defect seen in Δbb0744 mutant B. burgdorferi was due to the loss of BB0744. Taken together, these results suggest that BB0744 is necessary for tissue tropism, particularly in heart tissue, alters the ability of B. burgdorferi to disseminate efficiently, or both. Additional studies are warranted to address the mechanism employed by BB0744 that alters the pathogenic potential of B. burgdorferi.
authors.affiliation: Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center, Bryan, Texas, USA.
authors.forename: Beau
authors.initials: B
authors.lastname: Wager
authors.affiliation: Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center, Bryan, Texas, USA.
authors.forename: Dana K
authors.initials: DK
authors.lastname: Shaw
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Groshong
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Jon S
authors.initials: JS
authors.lastname: Blevins
authors.affiliation: Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center, Bryan, Texas, USA jskare@medicine.tamhsc.edu.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Skare
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D025065:Borrelia burgdorferi / Q000378:metabolism / Q000472:pathogenicity*; D004195:Disease Models, Animal; D005260:Female; D055785:Gene Knockdown Techniques; D015151:Immunoblotting; D008163:Luminescent Measurements; D008193:Lyme Disease / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018829:Adhesins, Bacterial