Epidemiological and Clinical Evidence for the Role of Toxins in S. aureus Human Disease

Bennett, Monique R.; Thomsen, Isaac

doi:10.3390/toxins12060408

Cited by 23 publications

(8 citation statements)

References 150 publications

(191 reference statements)

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“…Vaccine development has traditionally focused on stimulating antibody response. Anti- S. aureus antibodies play important roles in blocking toxins involved in immune cell lysis, and in providing opsonic help to phagocytes [ 38 ]. However, phase III clinical trials of two distinct vaccine candidates did not show efficacy in protection against bacteremia because of overreliance on antibody-mediated protective effect, suggesting that vaccines targeting T cell response may be preferable [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Vaccine Composition Formulated with a Novel Lactobacillus-Derived Exopolysaccharides Adjuvant Provided High Protection against Staphylococcus aureus

Zhang

Pan

et al. 2021

Vaccines

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A vaccine that effectively targets methicillin-resistant Staphylococcus aureus (MRSA) is urgently needed, and has been the focus of studies by numerous research groups, but with limited success to date. Recently, our team found that exopolysaccharides derived from probiotic Lactobacilluscasei strain WXD030 as an adjuvant-formulated OVA could upregulate IFN-γ and IL-17 expression in CD4+ T cells. In this study, we developed a vaccine (termed rMntC-EPS) composed of S. aureus antigen MntC and Lactobacillus casei exopolysaccharides, which conferred high levels of protection against S. aureus infection. Methods: Six–eight-week-old female mice were vaccinated with purified rMntC-EPS30. The immune protection function of rMntC-EPS30 was assessed by the protective effect of rMntC-EPS30 to S. aureus-induced pulmonary and cutaneous infection in mice, bacterial loads and H&E in injury site, and ELISA for inflammation-related cytokines. The protective mechanism of rMntC-EPS30 was assessed by ELISA for IgG in serum, cytokines in the spleen and lungs of vaccinated mice. In addition, flow cytometry was used for analyzing cellular immune response induced by rMntC-EPS30. For confirmation of our findings, three kinds of mice were used in this study: IL-17A knockout mice, IFN-γ knockout mice and TCRγ/δ knockout mice. Results: rMntC-EPS30 conferred up to 90% protection against S. aureus pulmonary infection and significantly reduced the abscess size in the S. aureus cutaneous model, with clearance of the pathogen. The rMntC-EPS vaccine could induce superior humoral immunity as well as significantly increase IL-17A and IFN-γ production. In addition, we found that rMntC-EPS vaccination induced robust Th 17/γδ T 17 primary and recall responses. Interestingly, this protective effect was distinctly reduced in the IL-17A knockout mice but not in IFN-γ knockout mice. Moreover, in TCRγ/δ knockout mice, rMntC-EPS vaccination neither increased IL-17A secretion nor provided effective protection against S. aureus infection. Conclusions: These data demonstrated that the rMntC formulated with a novel Lactobacillus-derived Exopolysaccharides adjuvant provided high protection against Staphylococcus aureu. The rMntC-EPS vaccine induced γδ T cells and IL-17A might play substantial roles in anti-S. aureus immunity. Our findings provided direct evidence that rMntC-EPS vaccine is a promising candidate for future clinical application against S. aureus-induced pulmonary and cutaneous infection.

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Section: Discussionmentioning

confidence: 99%

Vaccine Composition Formulated with a Novel Lactobacillus-Derived Exopolysaccharides Adjuvant Provided High Protection against Staphylococcus aureus

Zhang

Pan

et al. 2021

Vaccines

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“…As highlighted above, pyogenic organisms are the most common causative pathogens of pediatric musculoskeletal infection with S. aureus being responsible for 40% to 90% of cases. 3,24 In addition to antibacterial resistance genes, S. aureus has acquired virulence factors to help the pathogen evade the host's cellular APR, 108,109 and as a result have been associated with elevated inflammatory responses in pediatric MSKI. 110 Though the incidence varies between patient populations, [111][112][113][114][115][116][117][118][119][120] two examples of virulence factors observed in community-associated MSSA and MRSA are Pantone Valentine Leukocidin (PVL) and Leukocidin AB (LukAB).…”

Section: Virulence Factors Drive Disease Severity Through Attacking T...mentioning

confidence: 99%

Pediatric Musculoskeletal Infection - An Update Through the Four Pillars of Clinical Care and Immunothrombotic Similarities With COVID-19

Moore‐Lotridge

Gibson

Duvernay

et al. 2020

Journal of the Pediatric Orthopaedic Society of North America

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Few conditions in pediatric orthopaedics provoke more apprehension than a child with a musculoskeletal infection (MSKI). In addition to potential for devastating complications, the infectious organisms, technology to diagnose MSKI and pharmacology to treat MSKI evolve continuously. For these reasons, it is essential that pediatric orthopaedic surgeons be up to date on the current and future MSKI practices. In this review, current and potential future practices are systematically reviewed categorized by the four main tasks of the care team treating MSKI: determining 1) that location of the infection 2) is it an infection, and if so, what is the organism 3) how severe is the infection and 4) how to treat the infection. Finally, considering current events, the philosophy and tools highlighted for use in MSKI are paralleled in COVID-19 (SARS-CoV-2).

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“…However, these studies have not yet generated promising results due to toxicity and/or low bioavailability. New options are now under study with a focus on biological molecules or compounds to interfere with toxins or toxin-regulator genes, constituting a new generation of promising antistaphylococcal treatments [17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Staphylococcus aureus Toxins: An Update on Their Pathogenic Properties and Potential Treatments

Ahmad-Mansour

Loubet

Pouget

et al. 2021

Toxins

120

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Staphylococcus aureus is a clinically important pathogen that causes a wide range of human infections, from minor skin infections to severe tissue infection and sepsis. S. aureus has a high level of antibiotic resistance and is a common cause of infections in hospitals and the community. The rising prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA), combined with the important severity of S. aureus infections in general, has resulted in the frequent use of anti-staphylococcal antibiotics, leading to increasing resistance rates. Antibiotic-resistant S. aureus continues to be a major health concern, necessitating the development of novel therapeutic strategies. S. aureus uses a wide range of virulence factors, such as toxins, to develop an infection in the host. Recently, anti-virulence treatments that directly or indirectly neutralize S. aureus toxins have showed promise. In this review, we provide an update on toxin pathogenic characteristics, as well as anti-toxin therapeutical strategies.

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Epidemiological and Clinical Evidence for the Role of Toxins in S. aureus Human Disease

Cited by 23 publications

References 150 publications

Vaccine Composition Formulated with a Novel Lactobacillus-Derived Exopolysaccharides Adjuvant Provided High Protection against Staphylococcus aureus

Vaccine Composition Formulated with a Novel Lactobacillus-Derived Exopolysaccharides Adjuvant Provided High Protection against Staphylococcus aureus

Pediatric Musculoskeletal Infection - An Update Through the Four Pillars of Clinical Care and Immunothrombotic Similarities With COVID-19

Staphylococcus aureus Toxins: An Update on Their Pathogenic Properties and Potential Treatments

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