The HtrA-Like Serine Protease PepD Interacts with and Modulates the Mycobacterium tuberculosis 35-kDa Antigen Outer Envelope Protein
Mycobacterium tuberculosis remains a significant global health
concern largely due to its ability to persist for extended periods within the
granuloma of the host. While residing within the granuloma, the tubercle bacilli
are likely to be exposed to stress that can result in formation of aberrant
proteins with altered structures. Bacteria encode stress responsive determinants
such as proteases and chaperones to deal with misfolded or unfolded proteins.
pepD encodes an HtrA-like serine protease and is thought to
process proteins altered following exposure of M. tuberculosis
to extra-cytoplasmic stress. PepD functions both as a protease and chaperone
in vitro, and is required for aspects of M.
tuberculosis virulence in vivo. pepD is directly
regulated by the stress-responsive two-component signal transduction system
MprAB and indirectly by extracytoplasmic function (ECF) sigma factor SigE. Loss
of PepD also impacts expression of other stress-responsive determinants in
M. tuberculosis. To further understand the role of PepD in
stress adaptation by M. tuberculosis, a proteomics approach was
taken to identify binding proteins and possible substrates of this protein.
Using subcellular fractionation, the cellular localization of wild-type and PepD
variants was determined. Purified fractions as well as whole cell lysates from
Mycobacterium smegmatis or M. tuberculosis
strains expressing a catalytically compromised PepD variant were
immunoprecipitated for PepD and subjected to LC-MS/MS analyses. Using this
strategy, the 35-kDa antigen encoding a homolog of the PspA phage shock protein
was identified as a predominant binding partner and substrate of PepD. We
postulate that proteolytic cleavage of the 35-kDa antigen by PepD helps maintain
cell wall homeostasis in Mycobacterium and regulates specific
stress response pathways during periods of extracytoplasmic stress.
For the full article visit: The HtrA-Like Serine Protease PepD Interacts with and Modulates the
Mycobacterium tuberculosis 35-kDa Antigen Outer Envelope
Syndicated from:PLoS ONE
Article is licensed under a Creative Commons Attribution License.