Nickel-Dependent Urease Enables Staphylococcus aureus Persistence in Acidic Kidney Environments Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Microbes
Microbes
Microbes, short for microorganisms, are tiny living organisms that are ubiquitous in the environment, including on and inside the human body. They play a crucial role in human health and disease, functioning within complex ecosystems in various parts of the body, such as the skin, mouth, gut, and respiratory tract. The human microbiome, which is […]
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was studied?
This study investigated the role of nickel-dependent urease in Staphylococcus aureus as a critical component of its acid stress response network. Specifically, the researchers assessed the function of the urease operon in enabling S. aureus to survive under acidic conditions, such as those encountered during phagocytosis or in the kidney during persistent infection. They further examined the operon’s regulatory control and tested whether urease activity is essential for long-term bacterial persistence in a murine model of kidney infection.
Who was studied?
The study utilized S. aureus USA300 LAC strain and its isogenic urease mutants in both in vitro and in vivo experiments. In vitro assays involved assessing bacterial survival and pH modulation in acidic media. For in vivo studies, a murine model of systemic infection was used, with bacterial burden assessed in kidney and liver tissues over time to evaluate persistence. Mice infected with urease-deficient strains were compared to those infected with wild-type strains.
Most important findingsMost important findings
The study demonstrated that the Staphylococcus aureus urease operon (ureABCEFGD) is essential for survival under acidic conditions, functioning independently of known urea transporters. Urease expression was shown to be transcriptionally regulated by two major systems: CcpA (carbon catabolite protein A), which links regulation to central metabolism, and Agr (accessory gene regulator), a quorum-sensing system; both systems responded to acidic pH by upregulating urease expression. In vitro experiments confirmed that urease-positive strains were capable of alkalinizing the surrounding medium and exhibited prolonged survival in acidic environments compared to urease-deficient mutants. In vivo studies using a murine model of systemic infection revealed that Staphylococcus aureus urease kidney persistence was impaired in mutants lacking urease, as these strains showed significantly reduced bacterial burden in the kidneys at 14 days post-infection. Interestingly, this requirement was tissue-specific, as urease was dispensable for initial colonization and survival in the liver, highlighting a niche-specific adaptation of S. aureus to acidic microenvironments such as the kidney.
Key implications
This study identifies urease as a key acid resistance mechanism in S. aureus, with critical implications for chronic infections where the microenvironment is acidic, such as in abscesses or kidneys. The findings suggest that Staphylococcus aureus urease kidney persistence depends on metabolic and quorum-sensing regulation under acid stress. These insights are highly relevant for microbiome signatures where S. aureus is enriched in acidic inflammatory niches. Moreover, this regulatory link may inform microbiome-targeted intervention (MBTI) strategies targeting persistent S. aureus reservoirs.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Urease
Urease is a nickel-dependent microbial enzyme that breaks down urea into ammonia, altering local pH and nitrogen availability. While essential for microbial survival in acidic niches and nutrient-limited environments, urease activity also contributes to conditions like ulcers, urinary stones, colitis, and hepatic encephalopathy.
Staphylococcus aureus (S. Aureus)
Staphylococcus aureus is a versatile skin and mucosal commensal that can transition into a highly virulent pathobiont. Known for its immune-evasive strategies, toxin production, and antibiotic resistance, it plays a significant role in chronic infections and microbiome imbalance.
Microbiome-Targeted Interventions (MBTIs)
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.