RESUMEN
Toxic shock syndrome toxin-1 (TSST-1) is a superantigen (SAg) produced by Staphylococcus aureus thought to be responsible for essentially all cases of menstrual-associated toxic shock syndrome (TSS). As a potent exotoxin, it is not surprising that S. aureus has evolved multiple systems to control expression of TSST-1. Although the accessory gene regulator (Agr) system is recognized to enhance TSST-1 expression, how Agr regulates TSST-1 is unclear. Using an agr-null mutant, complementation experiments demonstrated that Agr controls TSST-1 expression through the activity of the RNAIII effector molecule. RNAIII can repress translation of the repressor of toxins (Rot) regulator, and deletion of rot increased expression of TSST-1 during the exponential phase of growth. Deletion of agr did not affect rot transcription, but did result in overexpression of the Rot protein, and Rot was also shown to bind and positively regulate the rot promoter. Overexpression of Rot dramatically repressed TSST-1, and Rot bound directly to the TSST-1 promoter. Deletion of both agr and rot in S. aureus returned TSST-1 expression to wild-type levels. This work demonstrates that Agr, although widely considered to be an inducer of TSST-1, has evolved in combination with Rot, to restrict the expression of this potent SAg.
Asunto(s)
Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/genética , Enterotoxinas/genética , Choque Séptico/genética , Superantígenos/genética , Transactivadores/metabolismo , Proteínas Bacterianas/genética , Toxinas Bacterianas/inmunología , Toxinas Bacterianas/metabolismo , Enterotoxinas/inmunología , Enterotoxinas/metabolismo , Exotoxinas/inmunología , Regulación Bacteriana de la Expresión Génica/genética , Genes Reguladores/genética , Regiones Promotoras Genéticas , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Choque Séptico/metabolismo , Infecciones Estafilocócicas/genética , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Superantígenos/inmunología , Superantígenos/metabolismo , Transactivadores/genéticaRESUMEN
While survival after hematological malignancies in adolescent and young adult patients is improving, patients report poor oncofertility care. This population-based, retrospective, cohort study used data from the Ontario Cancer Registry and billing codes to identify fertility consultations for lymphoma patients between 2000 and 2018. Consultation trends across time and different patient and physician characteristics were analyzed. We identified 2088 patients and a consultation rate of 3.4% (increasing from 1% in 2000-2006 to 8% in 2014-2018). Patient parity and regional deprivation scores decreased rates. Despite mild improvement, there is ample missed opportunity for fertility discussions.