RESUMEN
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.
Asunto(s)
Transportador 1 de Casete de Unión a ATP/genética , Lipoproteínas HDL/sangre , Fosfatidilcolina-Esterol O-Aciltransferasa/genética , Infecciones Estafilocócicas/genética , Animales , Toxinas Bacterianas/genética , Biopelículas/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Lipoproteínas HDL/genética , Ratones , Ratones Noqueados , Neutrófilos/microbiología , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidad , Factores de Virulencia/genéticaRESUMEN
Relations among peritraumatic dissociation, PTSD severity, event-related fear (i.e. fear experienced during traumatic event) about death, and event-related fear about losing control were examined in the current study. Particular emphasis was placed on testing whether or not fears about death and losing control mediate the relation between peritraumatic dissociation and PTSD severity in a sample of 146 nontreatment-seeking university women. Results indicated that event-related fears about death and losing control accounted for the relation between peritraumatic dissociation and PTSD severity; that is, the effect of peritraumatic dissociation on PTSD severity was eliminated after controlling for these fears. Speculations about findings are discussed.
