The Spx stress regulator confers high-level β-lactam resistance and decreases susceptibility to last-line antibiotics in methicillin-resistant .

Infections caused by methicillin-resistant (MRSA) are a leading cause of mortality worldwide. MRSA has acquired resistance to next-generation β-lactam antibiotics through the horizontal acquisition of the resistance gene. Development of high resistance is, however, often associated with additional mutations in a set of chromosomal core genes, known as potentiators, which, through poorly described mechanisms, enhance resistance.

A critical role for staphylococcal nitric oxide synthase in controlling flavohemoglobin toxicity.

Most coagulase-negative staphylococcal species, including the opportunistic pathogen Staphylococcus epidermidis, struggle to maintain redox homeostasis and grow under nitrosative stress. Under these conditions, growth can only resume once nitric oxide (NO) is detoxified by the flavohemoglobin Hmp. Paradoxically, S.

Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in stationary phase.

The transition from growth to stationary phase is a natural response of bacteria to starvation and stress. When stress is alleviated and more favorable growth conditions return, bacteria resume proliferation without a significant loss in fitness. Although specific adaptations that enhance the persistence and survival of bacteria in stationary phase have been identified, mechanisms that help maintain the competitive fitness potential of nondividing bacterial populations have remained obscure.

Staphylococcus aureus ATP Synthase Promotes Biofilm Persistence by Influencing Innate Immunity.

is a major cause of prosthetic joint infection (PJI), which is characterized by biofilm formation. biofilm skews the host immune response toward an anti-inflammatory profile by the increased recruitment of myeloid-derived suppressor cells (MDSCs) that attenuate macrophage proinflammatory activity, leading to chronic infection. A screen of the Nebraska Transposon Mutant Library identified several hits in the ATP synthase operon that elicited a heightened inflammatory response in macrophages and MDSCs, including , which encodes the alpha subunit of ATP synthase.

Lactate production by Staphylococcus aureus biofilm inhibits HDAC11 to reprogramme the host immune response during persistent infection.

Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI), resulting in considerable disability and prolonged treatment. It is known that host leukocyte IL-10 production is required for S. aureus biofilm persistence in PJI.

An integrated computational and experimental study to investigate Staphylococcus aureus metabolism.

Staphylococcus aureus is a metabolically versatile pathogen that colonizes nearly all organs of the human body. A detailed and comprehensive knowledge of staphylococcal metabolism is essential to understand its pathogenesis. To this end, we have reconstructed and experimentally validated an updated and enhanced genome-scale metabolic model of S.

Dual Gene Expression Analysis Identifies Factors Associated with Staphylococcus aureus Virulence in Diabetic Mice.

is a major human pathogen of the skin. The global burden of diabetes is high, with being a major complication of diabetic wound infections. We investigated how the diabetic environment influences skin infection and observed an increased susceptibility to infection in mouse models of both type I and type II diabetes.

Nitrite Derived from Endogenous Bacterial Nitric Oxide Synthase Activity Promotes Aerobic Respiration.

Macrophage-derived nitric oxide (NO·) is a crucial effector against invading pathogens. Yet, paradoxically, several bacterial species, including some pathogens, are known to endogenously produce NO· via nitric oxide synthase (NOS) activity, despite its apparent cytotoxicity. Here, we reveal a conserved role for bacterial NOS in activating aerobic respiration.