Urease is an essential component of the acid response network of Staphylococcus aureus and is required for a persistent murine kidney infection
Autor: | McKenzie K. Lehman, Robert Powers, Vinai Chittezham Thomas, Paul D. Fey, Tammy Kielian, Sujata S. Chaudhari, Kelsey J. Yamada, Fatema Bhinderwala, Kirk W. Foster, Chunyi Zhou |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
Arginine Urease Staphylococcus medicine.disease_cause Pathology and Laboratory Medicine Kidney Biochemistry chemistry.chemical_compound Mice Medicine and Health Sciences Urea Homeostasis Staphylococcus Aureus Amino Acids Biology (General) chemistry.chemical_classification 0303 health sciences biology Organic Compounds Monosaccharides Catabolism Hydrogen-Ion Concentration Staphylococcal Infections Enzymes Bacterial Pathogens Chemistry medicine.anatomical_structure Staphylococcus aureus Medical Microbiology CCPA Ureases Physical Sciences Female Kidney Diseases Pathogens Anatomy Basic Amino Acids Research Article Nitrogen QH301-705.5 Immunology Carbohydrates Microbiology 03 medical and health sciences Bacterial Proteins Ammonia Virology Genetics medicine Animals Molecular Biology Microbial Pathogens 030304 developmental biology Bacteria 030306 microbiology Organic Chemistry Chemical Compounds Organisms Biology and Life Sciences Proteins Kidneys Renal System RC581-607 Mice Inbred C57BL Enzyme Glucose Metabolism chemistry biology.protein Enzymology Parasitology Immunologic diseases. Allergy Acids |
Zdroj: | PLoS Pathogens, Vol 15, Iss 1, p e1007538 (2019) PLoS Pathogens |
ISSN: | 1553-7374 1553-7366 |
Popis: | 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. Author summary Urease has been reported to be crucial to bacteria in environmental adaptation, virulence, and defense against host immunity. Although the function of urease in S. aureus is not clear, recent evidence suggests that urease is important for acid resistance in various niches. Our study deciphered a function of S. aureus urease both in laboratory conditions and during host colonization. Furthermore, we uncovered the major components of the regulatory system that fine-tunes the expression of urease. Collectively, this study established the dual function of urease which serves as a significant part of the S. aureus acid response while also serving as an enzyme required for persistent kidney infections and potential subsequent staphylococcal metastasis. |
Databáze: | OpenAIRE |
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