NVC-422 Inactivates Staphylococcus aureus Toxins
| Autor: | Mark L Anderson, Dmitri Debabov, Andreas Jekle, Lu Wang, Christian Eitzinger, Timothy P. Shiau, Jungjoo Yoon, Suriani Abdul Rani, Meghan Zuck, Markus Nagl, Ramin Najafi, Charles Francavilla |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Staphylococcus aureus
Taurine medicine.medical_treatment Bacterial Toxins Virulence Enterotoxin Biology medicine.disease_cause Microbiology Enterotoxins Methionine Anti-Infective Agents Superantigen medicine Pharmacology (medical) Staphylococcal Protein A Mechanisms of Action: Physiological Effects Cell Proliferation Pharmacology Infectivity Superantigens Staphylococcal Infections Entry into host medicine.disease Exfoliatins Infectious Diseases Cytokine Immunology Cytokines Cytokine storm Oxidation-Reduction |
| Popis: | Bacterial pathogens have specific virulence factors (e.g., toxins) that contribute significantly to the virulence and infectivity of microorganisms within the human hosts. Virulence factors are molecules expressed by pathogens that enable colonization, immunoevasion, and immunosuppression, obtaining nutrients from the host or gaining entry into host cells. They can cause pathogenesis by inhibiting or stimulating certain host functions. For example, in systemic Staphylococcus aureus infections, virulence factors such as toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxin A (SEA), and staphylococcal enterotoxin B (SEB) cause sepsis or toxic shock by uncontrolled stimulation of T lymphocytes and by triggering a cytokine storm. In vitro , these superantigens stimulate the proliferation of human peripheral blood mononuclear cells (PBMC) and the release of many cytokines. NVC-422 ( N , N -dichloro-2,2-dimethyltaurine) is a broad-spectrum, fast-acting topical anti-infective agent against microbial pathogens, including antibiotic-resistant microbes. Using mass spectrometry, we demonstrate here that NVC-422 oxidizes methionine residues of TSST-1, SEA, SEB, and exfoliative toxin A (ETA). Exposure of virulence factors to 0.1% NVC-422 for 1 h prevented TSST-1-, SEA-, SEB-, and ETA-induced cell proliferation and cytokine release. Moreover, NVC-422 also delayed and reduced the protein A- and clumping factor-associated agglutination of S. aureus cultures. These results show that, in addition to its well-described direct microbicidal activity, NVC-422 can inactivate S. aureus virulence factors through rapid oxidation of methionines. |
| Databáze: | OpenAIRE |
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