title: Oligopeptide permease A5 modulates vertebrate host-specific adaptation of Borrelia burgdorferi.
abstract: Borrelia burgdorferi, the agent of Lyme disease, undergoes rapid adaptive gene expression in response to signals unique to its arthropod vector or vertebrate hosts. Among the upregulated genes under vertebrate host conditions is one of the five annotated homologs of oligopeptide permease A (OppA5, BBA34). A mutant lacking oppA5 was constructed in an lp25-deficient isolate of B. burgdorferi strain B31, and the minimal regions of infectivity were restored via a shuttle vector pBBE22 with or without an intact copy of bba34. Immunoblot analysis of the bba34 mutant revealed a reduction in the levels of RpoS, BosR, and CsrA(Bb) with a concomitant reduction in the levels of OspC, DbpA, BBK32, and BBA64. There were no changes in the levels of OspA, NapA, P66, and three other OppA orthologs. Quantitative transcriptional analysis correlated with the changes in the protein levels. However, the bba34 mutant displayed comparable infectivities in the C3H/HeN mice and the wild-type strain, despite the reduction in several pathogenesis-related proteins. Supplementation of the growth medium with increased levels of select components, notably sodium acetate and sodium bicarbonate, restored the levels of several proteins in the bba34 mutant to wild-type levels. We speculate that the transport of acetate appears to contribute to the accumulation of key metabolites, like acetyl phosphate, that facilitate the adaptation of B. burgdorferi to the vertebrate host by the activation of the Rrp2-RpoN-RpoS pathway. These studies underscore the importance of solute transport to host-specific adaptation of B. burgdorferi.
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors.forename: B V Subba
authors.initials: BV
authors.lastname: Raju
authors.forename: Maria D
authors.initials: MD
authors.lastname: Esteve-Gassent
authors.forename: S L Rajasekhar
authors.initials: SL
authors.lastname: Karna
authors.forename: Christine L
authors.initials: CL
authors.lastname: Miller
authors.forename: Tricia A
authors.initials: TA
authors.lastname: Van Laar
authors.forename: J
authors.initials: J
authors.lastname: Seshu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D025065:Borrelia burgdorferi / Q000235:genetics / Q000472:pathogenicity*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D054884:Host-Pathogen Interactions; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008193:Lyme Disease / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D008074:Lipoproteins; D037521:Virulence Factors; C046506:oligopeptide-binding protein, bacteria