Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.5.1.4 (
deaminase
)
5,113
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Brucella
, the causative agent of brucellosis, is a stealthy intracellular pathogen that is highly pathogenic to a range of mammals, including humans. The twin-arginine translocation (Tat) pathway transports folded proteins across the cytoplasmic membrane and has been implicated in virulence in many bacterial pathogens. However, the roles of the Tat system and related substrates in
Brucella
remain unclear. We report here that disruption of Tat increases the sensitivity of
Brucella melitensis
M28 to the membrane stressor sodium dodecyl sulfate (SDS), indicating cell envelope defects, as well as to EDTA. In addition, mutating Tat renders M28 bacteria more sensitive to oxidative stress caused by H
2
O
2
Further, loss of Tat significantly attenuates
B. melitensis
infection in murine macrophages
ex vivo
Using a mouse model for persistent infection, we demonstrate that Tat is required for full virulence of
B. melitensis
M28. Genome-wide
in silico
prediction combined with an
in vivo
amidase
reporter assay indicates that at least 23 proteins are authentic Tat substrates, and they are functionally categorized into solute-binding proteins, oxidoreductases, cell envelope biosynthesis enzymes, and others. A comprehensive deletion study revealed that 6 substrates contribute significantly to
Brucella
virulence, including an l,d-transpeptidase, an ABC transporter solute-binding protein, and a
methionine sulfoxide reductase
. Collectively, our work establishes that the Tat pathway plays a critical role in
Brucella
virulence.
...
PMID:The Twin-Arginine Translocation System Is Important for Stress Resistance and Virulence of Brucella melitensis. 3277 12
