Staphylococcus aureus infection
Staphylococcus aureus infection Main page
Staphylococcus aureus is the most common cause of staph infections. It is understood that amongst the general population 20–30% carry Staphylococci irrespective of being symptomatic. Staphylococcus aureus is associated with a number of illnesses including insignificant infections of the skin, like furuncles, impetigo, folliculitis, pimples, abscesses, boils, cellulitis ,carbuncles and scalded skin syndrome. It can also lead to various conditions that can be life-threatening such as endocarditis, toxic shock syndrome (TSS), meningitis, pneumonia, osteomyelitis, and septicemia. It can involve soft tissue, skin, joints, respiratory, musculoskeletal and cardiovascular systems. It is also known to cause nosocomial infections very commonly. Post surgical infections of the wound is also caused by Staphylococcus aureus.
S. aureus was discovered in 1880 by Sir Alexander Ogston, a surgeon from Aberdeen, Scotland, in pus from surgical abscesses. Moore than 500,000 patients in the US acquire a staphylococcal infection every year.
Staphylococcal infections can be classified according to the various organ systems involved. Staphylococcal infections may encompass skin and soft tissue, respiratory system, parroted glands, gastrointestinal system, eyes, musculoskeletal system, blood and cardiovascular system, central nervous system and urinary system.
Staphylococcus aureus is a highly virulent bacteria that has been recognized as a cause of a wide variety of diseases in humans. Approximately 60% of humans are colonized with Staphylococcus aureus (the nasal membranes and skin are the common habitat). Several strains of Staphylococcus aureus bacteria exist. The characteristic attribute of a particular strain such as toxins and extracellular factors, invasive properties (such as adherence, biofilm formation, and resistance to phagocytosis), as well as the immune defense mechanisms of the host, majorly determine the pathogenesis of Staphylococcus aureus infection. Staphylococcus aureus causes several infections ranging from mild infections to invasive diseases that are life threatening. Infections caused by Staphylococcus aureus include skin and soft tissue infections, osteomyelitis, food poisoning, pneumonia, infective endocarditis and sepsis. Some of the virulence factors that have been recognized in the pathogenesis of Staphylococcus aureus infections include:
- Staphylococcal superantigens (SAgs)
- These have been strongly implicated in a wide range of illnesses such as toxic shock syndrome and staphylococcal food poisoning.
- Several studies also suggest staphylococcal superantigens play a role in diseases such as atopic dermatitis, some forms of psoriasis, Kawasaki disease, and chronic rhinosinusitis.
- Staphylococcal superantigens are exotoxins with more than 20 distinct types, and most staphylococcus aureus strains encode many superantigen gene. Staphylococcus superantigens include staphylococcal enterotoxins, staphylococcal enterotoxin-like proteins, and toxic shock syndrome toxin-1.
- Staphylococcal enterotoxins cause food poisoning via ingestion of contaminated food. These enterotoxins have a very high stability and they are not easily denatured by heat and low pH (mild cooking or food digestion in the stomach cannot easily eradicate these toxins).
- Unlike most conventional peptides that stimulate roughly 1% of naive T-cells, a staphylococcal superantigen can simultaneously activate a large proportion of T lymphocytes (up to 20%).
- Staphylococcal superantigens are distinct because of their ability to bypass highly specific antigen-driven interaction between T-cells and antigen presenting cells.
- The superantigens can uniquely activate T lymphocytes by directly crosslinking certain TCR Vβ (T cell receptor β-chain variable domain).
- Numerous superantigen-activated T cells can then release several proinflammatory cytokines (this can lead to a “cytokine storm” phenomenon in severe cases, as seen in toxic shock syndrome). Superantigens also activate antigen presenting cells and this contributes to cytokine release.
- Alpha-hemolysin (α-toxin)
- This has been implicated in skin and soft tissue infections, and invasive Staphylococcus aureus diseases.
- It is a pore-forming cytotoxin, it forms transmembrane pores on the surface of target cells.
- Imbalance in ion homeostasis occur as a result of the pore formation (efflux of potassium cations and ATP or influx of calcium ions). This eventually result in cell death. Alpha-toxin targets a variety of cell types including epithelial and endothelial cells, platelets and blood cells.
- Alpha-hemolysin activates alpha-hemolysin receptor (a disintegrin and metalloprotease 10), contributing to proteolysis of E-cadherin. This results in the disruption of the adherens junction in the epithelial layer. Remodeling of the epithelial layer occurs and pathogen dissemination ensues.
- Proteolysis of the extracellular domain of vascular endothelial cadherin can also occur, contributing to the breach of blood vessel endothelium integrity.
- Alpha-toxin has been shown to promote strong host inflammatory responses which has been linked to increased morbidity and mortality.
- Alpha-toxin can activate intracellular host sensor molecules such as nucleotide-binding domain leucine-rich repeat containing (NLR) family (NLRC2 and NLRP3).
- The activation of the NLRP3 inflammasome by alpha-toxin and costimulation of NLRC2 by alpha-toxin and muramyl dipeptide, trigger the activation of caspase 1. This subsequently result in the activation of proinflammatory cytokine IL-1β which majorly contributes to the influx of polymorphonuclear leukocytes to the site of infection.
- Sizes of abscesses have been shown to significantly reduce following functional inactivation of the gene encoding alpha-hemolysin.
- Bicomponent leukocidins
- These include Panton-Valentine leukocidin (LukF-PV and LukS-PV), γ-hemolysins (HlgAB and HlgCB), LukED, and LukAB.
- Similar to the alpha-toxin, leukocidins are also Staphylococcus aureus pore-forming toxins.
- More than one leukocidin is often encoded by a S. aureus strain, and different leukocidins can target the same cell types and receptors.
- Leukocidins have been associated with staphylococcal skin and soft tissue infections, bacteremia, severe pneumonia.
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