| First Author | Hommes JW | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 15357 |
| PubMed ID | 34321507 | Mgi Jnum | J:359848 |
| Mgi Id | MGI:6740098 | Doi | 10.1038/s41598-021-94651-1 |
| Citation | Hommes JW, et al. (2021) High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins. Sci Rep 11(1):15357 |
| abstractText | Staphylococcus aureus virulence has been associated with the production of phenol-soluble modulins (PSMs). These PSMs have distinct virulence functions and are known to activate, attract and lyse neutrophils. These PSM-associated biological functions are inhibited by lipoproteins in vitro. We set out to address whether lipoproteins neutralize staphylococcal PSM-associated virulence in experimental animal models. Serum from both LCAT an ABCA1 knockout mice strains which are characterised by near absence of high-density lipoprotein (HDL) levels, was shown to fail to protect against PSM-induced neutrophil activation and lysis in vitro. Importantly, PSM-induced peritonitis in LCAT(-/-) mice resulted in increased lysis of resident peritoneal macrophages and enhanced neutrophil recruitment into the peritoneal cavity. Notably, LCAT(-/-) mice were more likely to succumb to staphylococcal bloodstream infections in a PSM-dependent manner. Plasma from homozygous carriers of ABCA1 variants characterized by very low HDL-cholesterol levels, was found to be less protective against PSM-mediated biological functions compared to healthy humans. Therefore, we conclude that lipoproteins present in blood can protect against staphylococcal PSMs, the key virulence factor of community-associated methicillin resistant S. aureus. |
