Effects of Staphylococcus aureus hemolysin toxins on blood cells and association with skin and soft tissue infections

Staphylococcus aureus (S. aureus) is gram positive, catalase positive cocci which belongs to the family of Staphylococcaceae and is long known as clinical and foodborne pathogen. The emergence of multidrug resistance strain of S. aureus which is methicillin resistant S. aureus (MRSA) challenges the health care system because it can cause wide variety of hospital and community acquired skin and soft tissue infections which are difficult to treat. The virulence of S. aureus is because of different factors which includes toxins, enzymes and superantigens. S. aureus produce variety of exotoxins, enterotoxins and exfoliative toxins which contributes to the virulence of S. aureus. Hemolysin toxins produce by S. aureus strains are associated with different skin and soft tissue infections (SSTIs) and can cause the lysis of RBCs. Hemolysins are regulated by accessory gene regulator (agr) and is required for the enhanced expression of virulence factors secreted by S. aureus. Hemolysins have leucolytic activity and can help in iron scavenging from host. The most important toxin is alpha hemolysin which can induce the apoptosis and cause the lysis of epithelial cells, erythrocytes and keratinocytes. Human immune cells are affected by beta hemolysin and gamma hemolysin is a biocomponent toxin. Delta hemolysin is low molecular weight exotoxin which belongs to the class of phenol soluble modulins. Keywords: MRSA, Exotoxins, Hemolysins, SSTIs

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Role of Antibodies in Protection Elicited by Active Vaccination with Genetically Inactivated Alpha Hemolysin in a Mouse Model of Staphylococcus aureus Skin and Soft Tissue Infections

Clinical and Vaccine Immunology ◽

10.1128/cvi.00051-14 ◽

2014 ◽

Vol 21 (5) ◽

pp. 622-627 ◽

Cited By ~ 19

Author(s):

Christopher P. Mocca ◽

Rebecca A. Brady ◽

Drusilla L. Burns

Keyword(s):

Staphylococcus Aureus ◽

Soft Tissue ◽

Murine Model ◽

Bacterial Colonization ◽

Passive Immunization ◽

The United States ◽

Soft Tissue Infections ◽

Content Type ◽

Alpha Hemolysin ◽

Active Vaccination

ABSTRACTDue to the emergence of highly virulent community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) infections,S. aureushas become a major threat to public health. A majority of CA-MRSA skin and soft tissue infections in the United States are caused byS. aureusUSA300 strains that are known to produce high levels of alpha hemolysin (Hla). Therefore, vaccines that contain inactivated forms of this toxin are currently being developed. In this study, we sought to determine the immune mechanisms of protection for this antigen using a vaccine composed of a genetically inactivated form of Hla (HlaH35L). Using a murine model of skin and soft tissue infections (SSTI), we found that BALB/c mice were protected by vaccination with HlaH35L; however, Jh mice, which are deficient in mature B lymphocytes and lack IgM and IgG in their serum, were not protected. Passive immunization with anti-HlaH35L antibodies conferred protection against bacterial colonization. Moreover, we found a positive correlation between the total antibody concentration induced by active vaccination and reduced bacterial levels. Animals that developed detectable neutralizing antibody titers after active vaccination were significantly protected from infection. These data demonstrate that antibodies to Hla represent the major mechanism of protection afforded by active vaccination with inactivated Hla in this murine model of SSTI, and in this disease model, antibody levels correlate with protection. These results provide important information for the future development and evaluation ofS. aureusvaccines.

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Protective efficacy of a novel alpha hemolysin subunit vaccine (AT62) against Staphylococcus aureus skin and soft tissue infections

Vaccine ◽

10.1016/j.vaccine.2016.09.061 ◽

2016 ◽

Vol 34 (50) ◽

pp. 6402-6407 ◽

Cited By ~ 23

Author(s):

Rajan P. Adhikari ◽

Christopher D. Thompson ◽

M. Javad Aman ◽

Jean C. Lee

Keyword(s):

Staphylococcus Aureus ◽

Soft Tissue ◽

Subunit Vaccine ◽

Protective Efficacy ◽

Soft Tissue Infections ◽

Alpha Hemolysin

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Characterization of Panton–Valentine leukocidin-positive Staphylococcus aureus from skin and soft tissue infections and wounds in Nigeria: a cross-sectional study

F1000Research ◽

10.12688/f1000research.15484.1 ◽

2018 ◽

Vol 7 ◽

pp. 1155 ◽

Cited By ~ 4

Author(s):

Olayemi O. Ayepola ◽

Nurudeen A. Olasupo ◽

Louis O. Egwari ◽

Frieder Schaumburg

Keyword(s):

Staphylococcus Aureus ◽

Soft Tissue ◽

Western Blotting ◽

Protein A ◽

Staphylococcal Protein A ◽

Soft Tissue Infections ◽

Accessory Gene ◽

Cross Sectional ◽

Panton Valentine Leukocidin ◽

Valentine Leukocidin

Background: Staphylococcus aureus is a significant pathogen implicated in numerous nosocomial and community-acquired infections. The Panton–Valentine leukocidin (PVL) can be associated with severe necrotizing diseases such as pneumonia, skin and soft tissue infection (SSTI). Methods: In total, 96 S. aureus isolates were obtained from patients presenting with wounds (n=48) and soft tissue infections (SSTIs, n=48). These were characterized based on their antimicrobial susceptibility profile, the possession of virulence genes (e.g. capsular type, PVL), accessory gene regulator (agr) type, and the staphylococcal protein A (spa) type. The production of the PVL protein was assessed by western blotting. Results: All isolates were susceptible to methicillin. The resistance was highest to penicillin (97.9%), followed by trimethoprim/sulfamethoxazole (85.4%) and tetracycline (10.4%). The PVL gene was found in 83.3% of isolates from SSTIs and in 79.2% of isolates from wound. Of these, 53 (68%) produced PVL as assessed by western blotting. The most prevalent spa type was the t084 (78.1%, n=75) and, majority of the isolates carried agr2 (82.3%, n=79). Conclusions: Prevalence of antibiotic resistant PVL-positive methicillin susceptible S. aureus strains has severe implications on PVL mediated infections.

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