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DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in
Bacillus anthracis.
Authors Laut CL, Leasure CS, Pi H, Carlin SM, Chu ML, Hillebrand GH, Lin HK, Yi XI,
Stauff DL, Skaar EP
Submitted By Submitted Externally on 3/9/2022
Status Published
Journal Infection and immunity
Year 2022
Date Published 1/1/2022
Volume : Pages 90 : e0056021
PubMed Reference 34748369
Abstract Bacillus anthracis is the causative agent of anthrax. This Gram-positive
bacterium poses a substantial risk to human health due to high mortality rates
and the potential for malicious use as a bioterror weapon. To survive within the
vertebrate host, B. anthracis relies on two-component system (TCS) signaling to
sense host-induced stresses and respond to alterations in the environment
through changes in target gene expression. HitRS and HssRS are cross-regulating
TCSs in B. anthracis that respond to cell envelope disruptions and high heme
levels, respectively. In this study, an unbiased and targeted genetic selection
was designed to identify gene products that are involved in HitRS and HssRS
signaling. This selection led to the identification of inactivating mutations
within dnaJ and clpX that disrupt HitRS- and HssRS-dependent gene expression.
DnaJ and ClpX are the substrate-binding subunits of the DnaJK protein chaperone
and ClpXP protease, respectively. DnaJ regulates the levels of HitR and HitS to
facilitate signal transduction, while ClpX specifically regulates HitS levels.
Together, these results reveal that the protein homeostasis regulators, DnaJ and
ClpX, function to maintain B. anthracis signal transduction activities through
TCS regulation.


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