Borrelia Host Adaptation Protein (BadP) Is Required for the Colonization of a Mammalian Host by the Agent of Lyme Disease.

Autor:	Smith TC 2nd; South Texas Center for Emerging Infectious Diseases (STCEID), Center of Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA., Helm SM; South Texas Center for Emerging Infectious Diseases (STCEID), Center of Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA., Chen Y; South Texas Center for Emerging Infectious Diseases (STCEID), Center of Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA., Lin YH; South Texas Center for Emerging Infectious Diseases (STCEID), Center of Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA., Rajasekhar Karna SL; South Texas Center for Emerging Infectious Diseases (STCEID), Center of Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA., Seshu J; South Texas Center for Emerging Infectious Diseases (STCEID), Center of Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA j.seshu@utsa.edu.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2018 Jun 21; Vol. 86 (7). Date of Electronic Publication: 2018 Jun 21 (Print Publication: 2018).
DOI:	10.1128/IAI.00057-18
Abstrakt:	Borrelia burgdorferi , the agent of Lyme disease (LD), uses host-derived signals to modulate gene expression during the vector and mammalian phases of infection. Microarray analysis of mutants lacking the B orrelia host ad aptation r egulator (BadR) revealed the downregulation of genes encoding enzymes whose role in the pathophysiology of B. burgdorferi is unknown. Immunoblot analysis of the badR mutants confirmed reduced levels of these enzymes, and one of these enzymes, encoded by bb0086 , shares homology to prokaryotic magnesium chelatase and Lon-type proteases. The BB0086 levels in B. burgdorferi were higher under conditions mimicking those in fed ticks. Mutants lacking bb0086 had no apparent in vitro growth defect but were incapable of colonizing immunocompetent C3H/HeN or immunodeficient SCID mice. Immunoblot analysis revealed reduced levels of proteins critical for the adaptation of B. burgdorferi to the mammalian host, such as OspC, DbpA, and BBK32. Both RpoS and BosR, key regulators of gene expression in B. burgdorferi , were downregulated in the bb0086 mutants. Therefore, we designated BB0086 the B orrelia host ad aptation p rotein (BadP). Unlike badP mutants, the control strains established infection in C3H/HeN mice at 4 days postinfection, indicating an early colonization defect in mutants due to reduced levels of the lipoproteins/regulators critical for initial stages of infection. However, badP mutants survived within dialysis membrane chambers (DMCs) implanted within the rat peritoneal cavity but, unlike the control strains, did not display complete switching of OspA to OspC, suggesting incomplete adaptation to the mammalian phase of infection. These findings have opened a novel regulatory mechanism which impacts the virulence potential of B burgdorferi . (Copyright © 2018 American Society for Microbiology.)
Databáze:	MEDLINE
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