title: Functional analysis of the Borrelia burgdorferi bba64 gene product in murine infection via tick infestation.
abstract: Borrelia burgdorferi, the causative agent of Lyme borreliosis, is transmitted to humans from the bite of Ixodes spp. ticks. During the borrelial tick-to-mammal life cycle, B. burgdorferi must adapt to many environmental changes by regulating several genes, including bba64. Our laboratory recently demonstrated that the bba64 gene product is necessary for mouse infectivity when B. burgdorferi is transmitted by an infected tick bite, but not via needle inoculation. In this study we investigated the phenotypic properties of a bba64 mutant strain, including 1) replication during tick engorgement, 2) migration into the nymphal salivary glands, 3) host transmission, and 4) susceptibility to the MyD88-dependent innate immune response. Results revealed that the bba64 mutant's attenuated infectivity by tick bite was not due to a growth defect inside an actively feeding nymphal tick, or failure to invade the salivary glands. These findings suggested there was either a lack of spirochete transmission to the host dermis or increased susceptibility to the host's innate immune response. Further experiments showed the bba64 mutant was not culturable from mouse skin taken at the nymphal bite site and was unable to establish infection in MyD88-deficient mice via tick infestation. Collectively, the results of this study indicate that BBA64 functions at the salivary gland-to-host delivery interface of vector transmission and is not involved in resistance to MyD88-mediated innate immunity.
authors.affiliation: Microbiology and Pathogenesis Activity, Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
authors.forename: Toni G
authors.initials: TG
authors.lastname: Patton
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Dietrich
authors.forename: Marc C
authors.initials: MC
authors.lastname: Dolan
authors.forename: Joseph
authors.initials: J
authors.lastname: Piesman
authors.forename: James A
authors.initials: JA
authors.lastname: Carroll
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gilmore
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics* / Q000502:physiology; D025065:Borrelia burgdorferi / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D018884:Ixodes; D008193:Lyme Disease / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D013984:Tick Infestations / Q000382:microbiology*
chemical_list: D000942:Antigens, Bacterial; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C562257:bba64 protein, Borrelia burgdorferi