The virulence factors of staphylococcus aureus

The virulence factors of staphylococcus aureus Staphylococcus aureus is faculatively anaerobic, catalase-positive, coagulase-positive, gram-positive cocci. It is non sporulating, non motile and non capsulated bacteria. 30% of Staphylococcus aureus can be found in skin, mucous of membrane and nasal passages in a healthy person as normal flora. However, Staphylococcus aureus infections are capable of leading to meningitis, pneumonia, osteomyetilis, spectic arthritis and septicemia. It is also difficult to treat Staphylococcus aureus infections if it is a methicillin resistant strain as the only antibiotic, vancomycin, is able to inhibit methicillin resistant Staphylococcus aureus(MRSA). Virulence Factors Virulence factors from Staphylococcus aureus can be structural or secreted products that lead to pathogenesis. They are classified into catogeries such as surface proteins, secreting toxins and superantigen toxin. Surface proteins in Staphylococcus aureus provide attachments to host tissues which will colonize and lead to infections. Such proteins are protein A/B which binds to immunoglobulin G, clumping factor A and B to help adherence to bacterial cells. [Plata, Rosato et al. 2009] Alpha-heamolysin, beta-heamolysin, gamma-heamolysin and Panton Valentine Leucocidine (PVL) are examples of secreting toxins which form pores in the host membrane and lyses the cells while staphylococcus enterotoxins weaken the host immune system and toxic shock syndrome toxin 1 causes toxic shock by food poisoning. These virulence factors that are produced [Plata, Rosato et al. 2009] by Staphylococcus aureus and often cause life-threatening diseases. These factors overcome and disguise themselves from th e body immune system so that Staphylococcus aureus can colonize and bind to connective tissues which lead to infections. They are also responsible for the symptoms of the disease. The main diagnostic features can be detected by having coagulase agglutination tests and test for the production of thermostable nuclease which break down DNA. [Greenwood, Slack et al. 2007] Exotoxins (TSST1-toxic shock syndrome toxin 1) TSST1 are one of the virulence factors that cause a variety of diseases in humans. TSST1 has short N-terminal ÃŽ ± helix which lead to ÃŽ ² barrel structure also known as B domain or oligosaccharide binding. It is then connected to C-terminal wall of the ÃŽ ² strands (Domain A). This structure cause cysteine loop which result in emetic activity. If there is no loop, TSST1 will be superantigenic [Orwin, Fitzgerald et al. May 2003]. As Staphylococcus aureus invade the body, TSST1 is produced in the bacteria and release to host. It then inhibits host immune responses. It crosses mucosal surfaces and reactivates bacterial cell wall induced arthritis. [Diages, Orwin et al. Jan 2000] TSST1 also stimulate proliferation of T cells. These T cells will not only increase its concentration in the body, but they are also unable to recognize specific antigen in the bacterial cells. Subsequently, T cells cannot eradicate Staphylococcus aureus. Therefore, TSST1 is also known as superantigenicity, py rogenicity and boost the lethality of the toxins. Acquired heart disease in children is often associated with TSST1. Also, TSST1 is linked to women who use tampons regularly as it increases the exposure to Staphylococcus aureus infections. TSST1 helps to release massive amount of cytokines which results in fever, rash, low blood pressure, tissue damage and shock. [Dermnet.org] Exotoxins (Panton Valentine Leucocidin-PVL) Panton Valentine Leucidin (PVL) is usually found in community-acquired Staphylococcus aureus (CA-MRSA). Tristan (2007) stated that it is categorized as bicomponent synergohymenotropic toxin which lyses host cell membrance and it targets on human polymorphonuclear neutrophils (PMN), monocytes and macrophages. Plasma membrane of myeloid cells form octamer pores and target leukocytes by Panton Valentine Leucidin [Kobayashi and Deleo 2009]. Inflammatory mediators such as leukotriene B4, IL-8 and histamine are released to the cell surrounding as PVL activates Ca2+ channels to open leading to calcium influx in PMN, monocytes and macrophages. As long as Ca2+ channels are opened and inflammatory mediators concentration is greatly rising, it is a fatal outcome. Thus, neutrophils, monocytes and macrophages lyses as pores form in their cell membranes and this usually results in toxic shock or refractory hypoxemia. Panton Valentine Leucidin plays a major role in severe necrotizing fasciitis, pne umonia, leukocyte destruction and tissue necrosis. [Libert, Batjom et al. Jan 2009] Staphylococcus enterotoxins-SE Staphylococcus enterotoxins are the common cause of food poisoning. As individual digests a large amount of Staphylococcus aureusthrough contaminated water or food, enterotoxins are produced. It has a major cross linking with major histocompability complex (MHC) class II antigen and T cell receptor (TCR) [Fraser and Proft 2008]. T cell receptor will recruit neutrophils and release a wide variety of inflammation mediators to the stomach and small intestine. Accumulation of inflammation mediators results in hyperemic mucosa and crypt extension develops in jejunum. The disruption of the lining of the small intestine influences the rate of absorption of substances. Thus, gastroenteritis forms and will bring about the systemic symptoms such as fever and hypotension.[ Diages, Orwin et al. Jan 2000]. Vomiting and diarrhea is also a common symptom in SE food poisoning. Food poisoning by Staphylococcus aureusis less severe than other infections by the same species. It is often self limiting a s well. [Diages, Orwin et al. Jan 2000] Protein A Protein A is characterized as a cell wall associated monomeric protein. [Gomez, Lee et al. 2004]. It has role in causing pneumonia by targeting polymorphonuclear (PMN) cell migration in the airway passages. Protein A binds to the Fc region of immunoglobulin G (IgG) and causes opsonization. [Greenwood, Slack et al. 2007]. It also phosphorylates mitogen activated protein kinases (MAPKs) as pro-inflammatory signaling. IL-8 is made and secreted out from epithelial cells. In addition, protein A also mimics TNF-ÃŽ ± (tumour necrosis factor ÃŽ ±) that will bind to TNFR1, which is distributed at airways (tumour necrosis factor receptor 1). This will recruit TRADD (TNFR1 associated death domain protein) and TRAF2 (TNF receptor associated factor 2). Both will be activated, protein A and TRAF2 with RIP1 will coimmunoprecipitate in the airways [Gomez, Lee et al. 2004]. Furthermore, protein A inhibits phagocytic engulfment. In the same paper, Gomez also stated that if Staphylococcus aureusis lacking in protein A or TNFR1, bacterial virulence will be lower and accumulation of PMN in the lung will be decrease as well. It is harmless to activate PMN as it is to protect the lung, however, when there is an increase in protein A binding to PMN, PMN is activated and enhancing the inflammatory mediators to be released in the airways. Therefore, an increase in protein A will generate a greater inflammatory response and subsequently pneumonia develops. Staphylokinase (SAK) Staphylokinase is an enzyme that produces by Staphylococcus aureus. When staphylokinase is released from Staphylococcus aureus and targeted to neutrophils, ÃŽ ±-defensins is produced and followed by neutralization of short peptides by Staphylococcus aureus. This results in inhibition of bactericidal effects of defensins by the activation of plasminogen and staphylokinase increases bacterial infection process. [Bergmann and Hammerschmidt 2007] Plasminogen is tightly regulated and it is a part of fibrinolysis mechanism which coagulates fibrin when a blood vessel is injured. Staphylococcus aureus changes plasminogen to fibrin with the help of fibrin as co-factor. Staphylokinase is encoded by the Sak gene and regulated by the agr gene. Its structure has a central ÃŽ ±-helix and 5 ÃŽ ² sheet strands. [Bokarewa, Jin et al. 2006]. Once neutophils is bound to the central ÃŽ ±-helix, it induces conformational changes. Consequently, plasminogen is converted to plasmin. Fibrin clots is then bro ken down by plasmin and kept the infection localized. Staphylokinase-plasminogen complexes also help Staphylococcus aureus to enter the host tissues. Furthermore, Maria stated that if 2 staphylokinase form a dimer due to the central ÃŽ ±-helical, it will reduce antigenicity. Several binding sites to neutrophils can be found in staphylokinase. This will induced in releasing of ÃŽ ±-defensins and affect the bactericidal properties as peptides are being neutralized. Staphylococcus aureusis then resistant to phagocytosis by neutrophils. [Bokarewa, Jin et al. 2006]. Staphylokinase infections are usually found in sepsis, immunocompromised and elderly patients as they are more prone to Staphylococcus aureus. Antibiotics are the usual therapy of these infections. Virulence Factors in Staphylococcus aureusare the main components that causing life threatening diseases. It is mostly the mediators released by the immune system gives the symptoms for the diseases. If there are any mutations in these virulence factors, it will be less virulent to the bacteria and the symptoms of disease will lessen as these virulence factors will not target neutrophils, macrophages and other immune system components. Therefore, inflammation mediators are not released in a great amount at once.