Published Research - 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

Date of this Version

2019

Citation

PLoS Pathog 15(1): e1007538

Comments

© 2019 Zhou et al.

Open access

https://doi.org/10.1371/journal.ppat.1007538

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.

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