Department of Chemistry
ORCID IDs
0000-0003-1278-5901
0000-0002-3033-8438
0000-0002-3335-5284
0000-0002-7886-0727
0000-0002-9609-152X
0000-0001-9948-6837
0000-0001-7624-670X
0000-0003-0939-6884
Document Type
Article
Date of this Version
2019
Citation
PLoS Pathog 15(1): e1007538
Abstract
Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic flux. In addition, it was determined that the endogenous urea derived from arginine is not a significant contributor to the intracellular nitrogen pool in non-acidic conditions. Furthermore, we found that during a murine chronic renal infection, urease facilitates S. aureus persistence by promoting bacterial fitness in the low-pH, urea-rich kidney. Overall, our study establishes that urease in S. aureus is not only a primary component of the acid response network but also an important factor required for persistent murine renal infections.
Included in
Analytical Chemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Other Chemistry Commons
Comments
© 2019 Zhou et al.
Open access
https://doi.org/10.1371/journal.ppat.1007538