Methicillin Resistance Elements in the Canine Pathogen and Their Association with the Peptide Toxin PSM-mec.

is a frequent cause of infections in dogs. Infectious isolates of this coagulase-positive staphylococcal species are often methicillin- and multidrug-resistant, which complicates therapy. In staphylococci, methicillin resistance is encoded by determinants found on mobile genetic elements called Staphylococcal Chromosome Cassette (SCC), which, in addition to methicillin resistance factors, sometimes encode additional genes, such as further resistance factors and, rarely, virulence determinants.

Virulence Mechanisms of Staphylococcal Animal Pathogens.

Staphylococci are major causes of infections in mammals. Mammals are colonized by diverse staphylococcal species, often with moderate to strong host specificity, and colonization is a common source of infection. Staphylococcal infections of animals not only are of major importance for animal well-being but have considerable economic consequences, such as in the case of staphylococcal mastitis, which costs billions of dollars annually.

Extensive remodelling of the cell wall during the development of bacteraemia.

The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope.

Extensive re-modelling of the cell wall during the development of bacteraemia.

The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope.

Exacerbation of allergic rhinitis by the commensal bacterium Streptococcus salivarius.

Allergic rhinitis (AR)-commonly called hay fever-is a widespread condition that affects the quality of life of millions of people. The pathophysiology of AR remains incompletely understood. In particular, it is unclear whether members of the colonizing nasal microbiota contribute to AR.

Identification and characterization of the pathogenic potential of phenol-soluble modulin toxins in the mouse commensal .

In contrast to the virulent human skin commensal , which secretes a plethora of toxins, other staphylococci have much reduced virulence. In these species, commonly the only toxins are those of the phenol-soluble modulin (PSM) family. PSMs are species-specific and have only been characterized in a limited number of species.

Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides.

Previously either regarded as insignificant or feared as potential sources of infection, the bacteria living on our skin are increasingly recognized for their role in benefitting human health. Skin commensals modulate mucosal immune defenses and directly interfere with pathogens; however, their contribution to the skin's physical integrity is less understood. Here, we show that the abundant skin commensal Staphylococcus epidermidis contributes to skin barrier integrity.

Rapid pathogen-specific recruitment of immune effector cells in the skin by secreted toxins.

Swift recruitment of phagocytic leucocytes is critical in preventing infection when bacteria breach through the protective layers of the skin. According to canonical models, this occurs via an indirect process that is initiated by contact of bacteria with resident skin cells and which is independent of the pathogenic potential of the invader. Here we describe a more rapid mechanism of leucocyte recruitment to the site of intrusion of the important skin pathogen Staphylococcus aureus that is based on direct recognition of specific bacterial toxins, the phenol-soluble modulins (PSMs), by circulating leucocytes.

Bacterial virulence plays a crucial role in MRSA sepsis.

Bacterial sepsis is a major global cause of death. However, the pathophysiology of sepsis has remained poorly understood. In industrialized nations, Staphylococcus aureus represents the pathogen most commonly associated with mortality due to sepsis.

Pathogenicity and virulence of .

is one of the most frequent worldwide causes of morbidity and mortality due to an infectious agent. This pathogen can cause a wide variety of diseases, ranging from moderately severe skin infections to fatal pneumonia and sepsis. Treatment of infections is complicated by antibiotic resistance and a working vaccine is not available.

Contribution of Staphylococcal Enterotoxin B to Staphylococcus aureus Systemic Infection.

Staphylococcal enterotoxin B (SEB), which is produced by the major human pathogen, Staphylococcus aureus, represents a powerful superantigenic toxin and is considered a bioweapon. However, the contribution of SEB to S. aureus pathogenesis has never been directly demonstrated with genetically defined mutants in clinically relevant strains.

Role of Phenol-Soluble Modulins in Staphylococcus epidermidis Biofilm Formation and Infection of Indwelling Medical Devices.

Phenol-soluble modulins (PSMs) are amphipathic, alpha-helical peptides that are secreted by staphylococci in high amounts in a quorum-sensing-controlled fashion. Studies performed predominantly in Staphylococcus aureus showed that PSMs structure biofilms, which results in reduced biofilm mass, while it has also been reported that S. aureus PSMs stabilize biofilms due to amyloid formation.

Resistance to leukocytes ties benefits of quorum sensing dysfunctionality to biofilm infection.

Social interactions play an increasingly recognized key role in bacterial physiology. One of the best studied is quorum sensing (QS), a mechanism by which bacteria sense and respond to the status of cell density. While QS is generally deemed crucial for bacterial survival, QS-dysfunctional mutants frequently arise in in vitro culture.

Pathogen elimination by probiotic Bacillus via signalling interference.

Probiotic nutrition is frequently claimed to improve human health. In particular, live probiotic bacteria obtained with food are thought to reduce intestinal colonization by pathogens, and thus to reduce susceptibility to infection. However, the mechanisms that underlie these effects remain poorly understood.

Basis of Virulence in Enterotoxin-Mediated Staphylococcal Food Poisoning.

The enterotoxins are a superfamily of secreted virulence factors that share structural and functional similarities and possess potent superantigenic activity causing disruptions in adaptive immunity. The enterotoxins can be separated into two groups; the classical (SEA-SEE) and the newer (SEG-SEY and counting) enterotoxin groups. Many members from both these groups contribute to the pathogenesis of several serious human diseases, including toxic shock syndrome, pneumonia, and sepsis-related infections.

Antimicrobial Peptide Resistance Mechanism Contributes to Staphylococcus aureus Infection.

Antimicrobial peptides (AMPs) constitute an important part of innate host defense. Possibly limiting the therapeutic potential of AMPs is the fact that bacteria have developed AMP resistance mechanisms during their co-evolution with humans. However, there is no direct evidence that AMP resistance per se is important during an infection.

Phenol-Soluble Modulin Toxins of .

Coagulase-negative staphylococci (CoNS) are important nosocomial pathogens and the leading cause of sepsis. The second most frequently implicated species, after , is . However, we have a significant lack of knowledge about what causes virulence of , as virulence factors of this pathogen have remained virtually unexplored.

Different drugs for bad bugs: antivirulence strategies in the age of antibiotic resistance.

The rapid evolution and dissemination of antibiotic resistance among bacterial pathogens are outpacing the development of new antibiotics, but antivirulence agents provide an alternative. These agents can circumvent antibiotic resistance by disarming pathogens of virulence factors that facilitate human disease while leaving bacterial growth pathways - the target of traditional antibiotics - intact. Either as stand-alone medications or together with antibiotics, these drugs are intended to treat bacterial infections in a largely pathogen-specific manner.

Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis.

Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS) with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin-resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown.

Bacterial Abscess Formation Is Controlled by the Stringent Stress Response and Can Be Targeted Therapeutically.

Cutaneous abscess infections are difficult to treat with current therapies and alternatives to conventional antibiotics are needed. Understanding the regulatory mechanisms that govern abscess pathology should reveal therapeutic interventions for these recalcitrant infections. Here we demonstrated that the stringent stress response employed by bacteria to cope and adapt to environmental stressors was essential for the formation of lesions, but not bacterial growth, in a methicillin resistant Staphylococcus aureus (MRSA) cutaneous abscess mouse model.

PSM-Mec-A Virulence Determinant that Connects Transcriptional Regulation, Virulence, and Antibiotic Resistance in Staphylococci.

PSM-mec is a secreted virulence factor that belongs to the phenol-soluble modulin (PSM) family of amphipathic, alpha-helical peptide toxins produced by Staphylococcus species. All known PSMs are core genome-encoded with the exception of PSM-mec, whose gene is found in specific sub-types of SCCmec methicillin resistance mobile genetic elements present in methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci. In addition to the cytolytic translational product, PSM-mec, the psm-mec locus encodes a regulatory RNA.

Adenoviral Expression of a Bispecific VHH-Based Neutralizing Agent That Targets Protective Antigen Provides Prophylactic Protection from Anthrax in Mice.

Bacillus anthracis, the causative agent of anthrax, secretes three polypeptides, which form the bipartite lethal and edema toxins (LT and ET, respectively). The common component in these toxins, protective antigen (PA), is responsible for binding to cellular receptors and translocating the lethal factor (LF) and edema factor (EF) enzymatic moieties to the cytosol. Antibodies against PA protect against anthrax.

Activator of G-Protein Signaling 3-Induced Lysosomal Biogenesis Limits Macrophage Intracellular Bacterial Infection.

Many intracellular pathogens cause disease by subverting macrophage innate immune defense mechanisms. Intracellular pathogens actively avoid delivery to or directly target lysosomes, the major intracellular degradative organelle. In this article, we demonstrate that activator of G-protein signaling 3 (AGS3), an LPS-inducible protein in macrophages, affects both lysosomal biogenesis and activity.

Functional characteristics of the Staphylococcus aureus δ-toxin allelic variant G10S.

Staphylococcus aureus δ-toxin is a member of the phenol-soluble modulin (PSM) peptide family. PSMs have multiple functions in staphylococcal pathogenesis; for example, they lyse red and white blood cells and trigger inflammatory responses. Compared to other PSMs, δ-toxin is usually more strongly expressed but has only moderate cytolytic capacities.