Affiliation:
1. 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
Abstract
ABSTRACT
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
.
Funder
HHS | NIH | National Institute of Allergy and Infectious Diseases
DOD | U.S. Army
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
7 articles.
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