Our skin is our first line of defense against environmental and pathogenic challenges. It is densely populated by a flora of bacteria, fungi, and viruses that normally interact with each other and ...with our immune system to promote skin health and homeostasis. Staphylococcus epidermidis is one of the most abundant bacterial colonizers of healthy human skin. While the field has historically assumed that all S. epidermidis isolates behave similarly, emerging evidence suggests that colonization by specific strains of S. epidermidis can either help or hurt the skin barrier depending on the context. In this short review, we discuss what is currently understood about S. epidermidis strain-level diversity and evaluate costs and benefits of S. epidermidis skin colonization. We challenge the current dogma that "all S. epidermidis strains behave equally" and posit that behavior is in fact highly context and strain dependent. Finally, in light of current proposals to use skin commensals as nonantibiotic treatments for acute or chronic skin diseases, we conclude that more work is urgently needed to fully understand the pathogenic and protective roles of commensals before we use them therapeutically.
The coagulase-negative bacterium Staphylococcus epidermidis is a member of the human skin microbiota. S. epidermidis is not merely a passive resident on skin but actively primes the cutaneous immune ...response, maintains skin homeostasis and prevents opportunistic pathogens from causing disease via colonization resistance. However, it is now appreciated that S. epidermidis and its interactions with the host exist on a spectrum of potential pathogenicity derived from its high strain-level heterogeneity. S. epidermidis is the most common cause of implant-associated infections and is a canonical opportunistic biofilm former. Additional emerging evidence suggests that some strains of S. epidermidis may contribute to the pathogenesis of common skin diseases. Here, we highlight new developments in our understanding of S. epidermidis strain diversity, skin colonization dynamics and its multifaceted interactions with the host and other members of the skin microbiota.
•Phagocytes play both protective and detrimental roles in containing bloodstream S. aureus.•S. aureus hijacks the host coagulation system and uses it to bind host endothelium.•Strategies used by S. ...aureus to cause host damage are highly strain-dependent.•Multiple regulatory systems control S. aureus bloodstream infections, including Agr, ArlRS, and MgrA.
Staphylococcus aureus is an opportunistic pathogen that normally colonizes the human anterior nares. At the same time, this pathogen is one of the leading causes of life-threatening bloodstream infections, such as sepsis and endocarditis. In this review we will present the current understanding of the pathogenesis of these invasive infections, focusing on the mechanisms of S. aureus clearance from the bloodstream by the immune system, and how this pathogen hijacks the host defense and coagulation systems and further interacts with the blood vessel endothelium. Additionally, we will delve into the regulatory mechanisms S. aureus employs during an invasive infection. These new insights into host–pathogen interactions show promising avenues for the development of novel therapies for treating bloodstream infections.
is a Gram-positive opportunistic pathogen that has evolved a complex regulatory network to control virulence. One of the main functions of this interconnected network is to sense various ...environmental cues and respond by altering the production of virulence factors necessary for survival in the host, including cell surface adhesins and extracellular enzymes and toxins. Of these
regulatory systems, one of the best studied is the accessory gene regulator (
), which is a quorum-sensing system that senses the local concentration of a cyclic peptide signaling molecule. This system allows
to sense its own population density and translate this information into a specific gene expression pattern. Besides
, this pathogen uses other two-component systems to sense specific cues and coordinates responses with cytoplasmic regulators of the SarA protein family and alternative sigma factors. These divergent regulatory systems integrate the various environmental and host-derived signals into a network that ensures optimal pathogen response to the changing conditions. This article gives an overview of the most important and best-studied
regulatory systems and summarizes the functions of these regulators during host interactions. The regulatory systems discussed include the
quorum-sensing system; the SaeRS, SrrAB, and ArlRS two-component systems, the cytoplasmic SarA-family regulators (SarA, Rot, and MgrA); and the alternative sigma factors (SigB and SigH).
The agr quorum-sensing system of Staphylococcus aureus modulates the expression of virulence factors in response to autoinducing peptides (AIPs). Recent studies have suggested a role for the agr ...system in S. aureus biofilm development, as agr mutants exhibit a high propensity to form biofilms, and cells dispersing from a biofilm have been observed displaying an active agr system. Here, we report that repression of agr is necessary to form a biofilm and that reactivation of agr in established biofilms through AIP addition or glucose depletion triggers detachment. Inhibitory AIP molecules did not induce detachment and an agr mutant was non-responsive, indicating a dependence on a functional, active agr system for dispersal. Biofilm detachment occurred in multiple S. aureus strains possessing divergent agr systems, suggesting it is a general S. aureus phenomenon. Importantly, detachment also restored sensitivity of the dispersed cells to the antibiotic rifampicin. Proteinase K inhibited biofilm formation and dispersed established biofilms, suggesting agr-mediated detachment occurred in an ica-independent manner. Consistent with a protease-mediated mechanism, increased levels of serine proteases were detected in detaching biofilm effluents, and the serine protease inhibitor PMSF reduced the degree of agr-mediated detachment. Through genetic analysis, a double mutant in the agr-regulated Aur metalloprotease and the SplABCDEF serine proteases displayed minimal extracellular protease activity, improved biofilm formation, and a strongly attenuated detachment phenotype. These findings indicate that induction of the agr system in established S. aureus biofilms detaches cells and demonstrate that the dispersal mechanism requires extracellular protease activity.
Skin health is influenced by the composition and integrity of the skin barrier. The healthy skin surface is an acidic, hypertonic, proteinaceous, and lipid-rich environment that microorganisms must ...adapt to for survival, and disruption of this environment can result in dysbiosis and increase risk for infectious diseases. This work provides a brief overview of skin barrier function and skin surface composition from the perspective of how the most common skin pathogen, Staphylococcus aureus, combats acid stress. Advancements in replicating this environment in the laboratory setting for the study of S. aureus pathogenesis on the skin, as well as future directions in this field, are also discussed.
Staphylococcus aureus is a major cause of nosocomial and community-acquired infections and represents a significant burden on the healthcare system. S. aureus attachment to medical implants and host ...tissue, and the establishment of a mature biofilm, play an important role in the persistence of chronic infections. The formation of a biofilm, and encasement of cells in a polymer-based matrix, decreases the susceptibility to antimicrobials and immune defenses, making these infections difficult to eradicate. During infection, dispersal of cells from the biofilm can result in spread to secondary sites and worsening of the infection. In this review, we discuss the current understanding of the pathways behind biofilm dispersal in S. aureus, with a focus on enzymatic and newly described broad-spectrum dispersal mechanisms. Additionally, we explore potential applications of dispersal in the treatment of biofilm-mediated infections.
Bacteria of the genus Staphylococcus are a prominent cause of acute and chronic infections. The ability of the staphylococci to establish biofilms has been linked to the persistence of chronic ...infections, which has drawn considerable interest from researchers over the past decade. Biofilms can be defined as sessile communities of surface‐attached cells encased in an extracellular matrix, and treatment of bacteria in this mode of growth is challenging due to the resistance of biofilm structures to both antimicrobials and host defenses. In this review of the literature, we introduce Staphylococcus aureus and Staphylococcus epidermidis biofilms and summarize current antibiotic treatment approaches for staphylococcal biofilm infections. We also review recent studies on alternative strategies for preventing biofilm formation and dispersing established biofilms, including matrix‐degrading enzymes, small‐molecule approaches, and manipulation of natural staphylococcal disassembly mechanisms. While research on staphylococcal biofilm development is still in its early stages, new discoveries in the field hold promise for improved therapies that target staphylococcal biofilm infections.
The staphylococci comprise a diverse genus of Gram-positive, nonmotile commensal organisms that inhabit the skin and mucous membranes of humans and other mammals. In general, staphylococci are benign ...members of the natural flora, but many species have the capacity to be opportunistic pathogens, mainly infecting individuals who have medical device implants or are otherwise immunocompromised. Staphylococcus aureus and Staphylococcus epidermidis are major sources of hospital-acquired infections and are the most common causes of surgical site infections and medical device-associated bloodstream infections. The ability of staphylococci to form biofilms in vivo makes them highly resistant to chemotherapeutics and leads to chronic diseases. These biofilm infections include osteomyelitis, endocarditis, medical device infections, and persistence in the cystic fibrosis lung. Here, we provide a comprehensive analysis of our current understanding of staphylococcal biofilm formation, with an emphasis on adhesins and regulation, while also addressing how staphylococcal biofilms interact with the immune system. On the whole, this review will provide a thorough picture of biofilm formation of the staphylococcus genus and how this mode of growth impacts the host.
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