Project description:Flagellar export apparatus protein, FliH, is involved in post-transcriptional regulation of FlaB, motility and virulence of the relapsing fever spirochete Borrelia hermsii
Project description:Borrelia hermsii is the most common cause of tickborne relapsing fever in North America. DNA sequences of the 16S-23S rDNA noncoding intergenic spacer (IGS) region were determined for 37 isolates of this spirochete. These sequences distinguished the 2 genomic groups of B. hermsii identified previously with other loci. Multiple IGS genotypes were identified among isolates from an island, which suggested that birds might play a role in dispersing these spirochetes in nature. In support of this theory, all stages of the tick vector Ornithodoros hermsi fed successfully on birds in the laboratory and advanced in their life cycle. B. hermsii produced a detectable spirochetemia in 1 chicken inoculated subcutaneously. Additional work is warranted to explore the role of birds as enzootic hosts for this relapsing fever spirochete.
Project description:The blacklegged tick Ixodes scapularis is the primary vector of the most prevalent vector-borne zoonosis in North America, Lyme disease (LD). Enzootic maintenance of the pathogen Borrelia burgdorferi by I. scapularis and small mammals is well documented, whereas its "cryptic" maintenance by other specialist ticks and wildlife hosts remains largely unexplored because these ticks rarely bite humans. We quantified B. burgdorferi infection in a cryptic bird-rabbit-tick cycle. Furthermore, we explored the role of birds in maintaining and moving B. burgdorferi strains by comparing their genetic diversity in this cryptic cycle to that found in cycles vectored by I. scapularis. We examined birds, rabbits, and small mammals for ticks and infection over a 4-year period at a focal site in Michigan, 90 km east of a zone of I. scapularis invasion. We mist netted 19,631 birds that yielded 12,301 ticks, of which 86% were I. dentatus, a bird-rabbit specialist. No resident wildlife harbored I. scapularis, and yet 3.5% of bird-derived ticks, 3.6% of rabbit-derived ticks, and 20% of rabbit ear biopsy specimens were infected with B. burgdorferi. We identified 25 closely related B. burgdorferi strains using an rRNA gene intergenic spacer marker, the majority (68%) of which had not been reported previously. The presence of strains common to both cryptic and endemic cycles strongly implies bird-mediated dispersal. Given continued large-scale expansion of I. scapularis populations, we predict that its invasion into zones of cryptic transmission will allow for bridging of novel pathogen strains to humans and animals.
Project description:Borrelia species are amino acid auxotrophs that utilize di- and tri- peptides obtained through their oligopeptide transport system to supply amino acids for replicative growth during their enzootic cycles. However, Borrelia species from both the Lyme disease (LD) and relapsing fever (RF) groups harbor an amino acid transport and catabolism system, the Arginine Deiminase System (ADI), that could potentially augment intracellular L-arginine required for growth. RF spirochetes contain a "complete", four gene ADI (arcA, B, D, and C) while LD spirochetes harbor arcA, B, and sometimes D but lack arcC (encoding carbamate kinase). In this study, we evaluated the role of the ADI system in bacterial survival and virulence and discovered important differences in RF and LD ADIs. Both in vitro and in a murine model of infection, B. hermsii cells significantly reduced extracellular L-arginine levels and that reduction was dependent on arginine deiminase expression. Conversely, B. burgdorferi did not reduce the concentration of L-arginine during in vitro growth experiments nor during infection of the mammalian host, suggesting a fundamental difference in the ability to directly utilize L-arginine compared to B. hermsii. Further experiments using a panel of mutants generated in both B. burgdorferi and B. hermsii, identified important differences in growth characteristics and ADI transcription and protein expression. We also found that the ADI system plays a key role in blood and spleen colonization in RF spirochetes. In this study we have identified divergent metabolic strategies in two closely related human pathogens, that ultimately impacts the host-pathogen interface during infection.