The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis.

Background: Staphylococcus aureus is the most common cause of life-threatening endovascular infections, including infective endocarditis (IE). These infections, especially when caused by methicillin-resistant strains (MRSA), feature limited therapeutic options and high morbidity and mortality rates.

Methods: Herein, we investigated the role of the purine biosynthesis repressor, PurR, in virulence factor expression and vancomycin (VAN) treatment outcomes in experimental IE due to MRSA.

Protocol for studying co-infection between SARS-CoV-2 and Staphylococcus aureus in vitro.

Bacterial co-infection is one of the most common complications of SARS CoV-2 infection. Here, we present a protocol for the in vitro study of co-infection between SARS CoV-2 and Staphylococcus aureus. We describe steps for quantifying viral and bacterial replication kinetics in the same sample, with the optional extraction of host RNA and proteins.

Autolysin-mediated peptidoglycan hydrolysis is required for the surface display of cell wall-anchored proteins.

Peptidoglycan hydrolases, or autolysins, play a critical role in cell wall remodeling and degradation, facilitating bacterial growth, cell division, and cell separation. In the so-called "major" autolysin, Atl, has long been associated with host adhesion; however, the molecular basis underlying this phenomenon remains understudied. To investigate, we used the type V glycopeptide antibiotic complestatin, which binds to peptidoglycan and blocks the activity of autolysins, as a chemical probe of autolysin function.

The protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling.

The Severe Acute Respiratory Syndrome Coronavirus 2 (CoV-2) pandemic has affected millions globally. A significant complication of CoV-2 infection is secondary bacterial co-infection, as seen in approximately 25% of severe cases. The most common organism isolated during co-infection is Here, we describe the development of an co-infection model where both viral and bacterial replication kinetics may be examined.

MRSA Isolates from Patients with Persistent Bacteremia Generate Nonstable Small Colony Variants within Macrophages and Endothelial Cells during Prolonged Vancomycin Exposure.

Staphylococcus aureus (especially methicillin-resistant S. aureus [MRSA]) is frequently associated with persistent bacteremia (PB) during vancomycin therapy despite consistent susceptibility . Strategic comparisons of PB strains versus those from vancomycin-resolving bacteremia (RB) would yield important mechanistic insights into PB outcomes.

Superantigens promote bloodstream infection by eliciting pathogenic interferon-gamma production.

is a foremost bacterial pathogen responsible for a vast array of human diseases. Staphylococcal superantigens (SAgs) constitute a family of exotoxins from that bind directly to major histocompatibility complex (MHC) class II and T cell receptors to drive extensive T cell activation and cytokine release. Although these toxins have been implicated in serious disease, including toxic shock syndrome, the specific pathological mechanisms remain unclear.

Nucleotide biosynthesis: the base of bacterial pathogenesis.

Most free-living organisms require the synthesis and/or acquisition of purines and pyrimidines, which form the basis of nucleotides, to survive. In most bacteria, the nucleotides are synthesized de novo and the products are used in many cell functions, including DNA replication, energy storage, and as signaling molecules. Due to their central role in the metabolism of bacteria, both nucleotide biosynthesis pathways have strong links with the virulence of opportunistic and bona fide bacterial pathogens.

Evolutionary and Functional Analysis of Coagulase Positivity among the Staphylococci.

The bacterial genus Staphylococcus comprises a large group of pathogenic and nonpathogenic species associated with an array of host species. Staphylococci are differentiated into coagulase-positive or coagulase-negative groups based on the capacity to promote clotting of plasma, a phenotype historically associated with the ability to cause disease. However, the genetic basis of this important diagnostic and pathogenic trait across the genus has not been examined to date.

s secreted lipases do not inhibit innate immune killing mechanisms.

causes an array of diseases in both humans and livestock. Pathogenesis is mediated by a plethora of proteins secreted by , many of which remain incompletely characterised. For example, abundantly secretes two isoforms of the enzyme lipase into the extracellular milieu, where they scavenge upon polymeric triglycerides.

Mutations in a Membrane Permease or Lead to 6-Thioguanine Resistance in Staphylococcus aureus.

We recently discovered that 6-thioguanine (6-TG) is an antivirulence compound that is produced by a number of coagulase-negative staphylococci. In Staphylococcus aureus, it inhibits purine biosynthesis and ribosomal protein expression, thus inhibiting growth and abrogating toxin production. Mechanisms by which S.

Coagulase-negative staphylococci release a purine analog that inhibits Staphylococcus aureus virulence.

Coagulase-negative staphylococci and Staphylococcus aureus colonize similar niches in mammals and conceivably compete for space and nutrients. Here, we report that a coagulase-negative staphylococcus, Staphylococcus chromogenes ATCC43764, synthesizes and secretes 6-thioguanine (6-TG), a purine analog that suppresses S. aureus growth by inhibiting de novo purine biosynthesis.

Staphylococcus aureus Lipase 1 Enhances Influenza A Virus Replication.

Influenza A virus (IAV) causes annual epidemics of respiratory disease in humans, often complicated by secondary coinfection with bacterial pathogens such as Here, we report that the secreted protein lipase 1 enhances IAV replication in primary cells, including human lung fibroblasts. The proviral activity of lipase 1 is dependent on its enzymatic function, acts late in the viral life cycle, and results in increased infectivity through positive modulation of virus budding. Furthermore, the proviral effect of lipase 1 on IAV is exhibited during infection of embryonated hen's eggs and, importantly, increases the yield of a vaccine strain of IAV by approximately 5-fold.

Purine Biosynthesis Is Required for Intracellular Growth of Staphylococcus aureus and for the Hypervirulence Phenotype of a Mutant.

is a noted human and animal pathogen. Despite decades of research on this important bacterium, there are still many unanswered questions regarding the pathogenic mechanisms it uses to infect the mammalian host. This can be attributed to it possessing a plethora of virulence factors and complex virulence factor and metabolic regulation.

Stress-induced inactivation of the Staphylococcus aureus purine biosynthesis repressor leads to hypervirulence.

Staphylococcus aureus is a significant cause of human infection. Here, we demonstrate that mutations in the transcriptional repressor of purine biosynthesis, purR, enhance the pathogenic potential of S. aureus.

Immunological Homeostasis at the Ovine Placenta May Reflect the Degree of Maternal Fetal Interaction.

Successful mammalian pregnancies are a result of complex physiological, endocrinological, and immunological processes that combine to create an environment where the mother is tolerant to the semi-allogeneic fetus. Our knowledge of the mechanisms that contribute to maternal tolerance is derived mainly from human and murine studies of haemochorial placentation. However, as this is the most invasive type of placentation it cannot be assumed that identical mechanisms apply to the less invasive epitheliochorial placentation found in other species such as ruminants.

Staphylococcus pseudintermedius Surface Protein L (SpsL) Is Required for Abscess Formation in a Murine Model of Cutaneous Infection.

is the leading cause of pyoderma in dogs and is often associated with recurrent skin infections that require prolonged antibiotic therapy. High levels of antibiotic use have led to multidrug resistance, including the emergence of epidemic methicillin-resistant clones. Our understanding of the pathogenesis of skin infection is very limited, and the identification of the key host-pathogen interactions underpinning infection could lead to the design of novel therapeutic or vaccine-based approaches for controlling disease.

The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function.

Bacterial superantigens (SAgs) cause Vβ-dependent T-cell proliferation leading to immune dysregulation associated with the pathogenesis of life-threatening infections such as toxic shock syndrome, and necrotizing pneumonia. Previously, we demonstrated that staphylococcal enterotoxin-like toxin X (SElX) from Staphylococcus aureus is a classical superantigen that exhibits T-cell activation in a Vβ-specific manner, and contributes to the pathogenesis of necrotizing pneumonia. Here, we discovered that SElX can also bind to neutrophils from human and other mammalian species and disrupt IgG-mediated phagocytosis.