AI Article Synopsis
- Cytolytic pore-forming toxins like alpha hemolysin (Hla) and leukotoxins are crucial for the pathogenicity of certain bacteria, killing immune cells and providing nutrients for growth.
- A mutation in the SaeS sensor enhances a strain's toxin activity independently from Hla, allowing it to lyse human red blood cells more effectively.
- Research shows that this Hla-independent activity relies on the gamma hemolysin A subunit and emphasizes the role of Sae and Agr systems in bacterial virulence, which is important for developing vaccines and treatments.
Article Abstract
Cytolytic pore-forming toxins including alpha hemolysin (Hla) and bicomponent leukotoxins play an important role in the pathogenesis of . These toxins kill the polymorphonuclear phagocytes (PMNs), disrupt epithelial and endothelial barriers, and lyse erythrocytes to provide iron for bacterial growth. The expression of these toxins is regulated by the two-component sensing systems Sae and Agr. Here, we report that a point mutation (L18P) in SaeS, the histidine kinase sensor of the Sae system, renders the Newman hemolytic activity fully independent of Hla and drastically increases the PMN lytic activity. Furthermore, this Hla-independent activity, unlike Hla itself, can lyse human erythrocytes. The Hla-independent activity towards human erythrocytes was also evident in USA300, however, under strict control. Gene knockout studies revealed that this Hla-independent Sae-regulated activity was entirely dependent on gamma hemolysin A subunit (HlgA). In contrast, hemolytic activity of Newman towards human erythrocytes from HlgAB resistant donors was completely dependent on . The culture supernatant from Newman could be neutralized by antisera against two vaccine candidates based on LukS and LukF subunits of Panton-Valentine leukocidin but not by an anti-Hla neutralizing antibody. These findings display the complex involvement of Sae and Agr systems in regulating the virulence of and have important implications for vaccine and immunotherapeutics development for disease in humans.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162840 | PMC |
| http://dx.doi.org/10.3390/toxins10090377 | DOI Listing |
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