SHIGA TOXIN PRODUCING ESCHERICHIA COLI INFECTIONS, INSIGHTS INTO POSSIBLE COMPLICATIONS DURING PREGNANCY

SACERDOTI, FLAVIA

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAI-SAFIS 2018; 2018

Sociedad Argentina de Investigación Clínica-Sociedad Argentina de Inmunología-Sociedad Argentina de Fisiología

Infections during pregnancy are associated with adverse outcomes including miscarriage, premature rupture of membranes, preterm birth, growth restriction and stillbirth.Shiga toxin producing Escherichia coli (STEC) is a group of gastrointestinal bacteria that causes diarrhea, hemorrhagic colitis, and can develop a systemic complication known as hemolytic uremic syndrome (HUS). Themain virulence factor of STEC is Shiga toxin (Stx) which crosses the intestinal barrier, reaches the bloodstream and damages the target cells through binding the globotriaosylceramide (Gb3) receptor. Among the various Stx subtypes, Stx1 and Stx2 are of eminent clinical importance in human infections being Stx2 associated with more severe cases than Stx1. STEC infections affect mainly young children, although the large HUS outbreak with a Stx2-producing enteroaggregative E. coli strain in Europe in 2011 involved more adults than children, and women were overrepresented. We propose that symptomatic or asymptomatic STEC infections during pregnancy may cause maternal or fetal damage mediated by Stx2. Ours studies in rats showed that Stx2 binds the utero-placental unit and causes adverse pregnancy outcomes. Stx2 during early pregnancy induces decidual necrosis, promotes a pro-inflammatory environmentthat together with high hypoxia levels leads to pregnancy loss. In addition, we demonstrated that an active immunity against Stx2 protects the mother and fetus from Stx2 cytotoxicity. On the other hand, Stx2 during late pregnancy induces placental abruption, intrauterine hemorrhage and premature delivery of dead fetuses. In vitro studies involving human trophoblast cells indicate thatStx2 produces loss of cell viability, including apoptosis, and impairs trophoblast cell migration and invasion. Additionally, Stx2 modulates MMP2 activity suggesting that metalloproteinases can be affected by the toxin. Recentstudies suggest that nitric oxide may be related to damages induced by Stx2. Although nowadays there are not reports indicating that Stx2 affect pregnancy in humans, our data suggest that Stx2 may generate complications during gestation.