Role of the SepA serine protease in the cytotoxic and proinflammatory activities induced by enteroaggregative Escherichia coli

Abstract

Enteroaggregative Escherichia coli (EAEC) is an emerging enteropathogen among the bacterial agents of diarrhea worldwide. Nowadays a strong association has been reported between EAEC and acute and persistent diarrhea in children in both developing and developed countries. In 2011 a large outbreak of diarrhea, which affected several countries in Europe, was caused by a strain of Shiga toxin-producing E. coli. Sequencing this strain showed that it was an EAEC that acquired a phage encoding Stx2, a characteristic of Shiga toxin-producing E. coli (STEC). This strain has several virulence factors including the SPATE proteins (Serine Protease Autotransporters of Enterobacteriaceae), which are secreted to the extracellular milieu by the type V secretion system, also known as autotransporter system. The SPATEs are distributed among the Enterobacteriaceae family and are defined as important virulence factors in many pathogens. SepA is a SPATE, originally described in Shigella flexneri 2a and later in EAEC, which belong to the class 2 SPATE that include autotransporters with immunomodulatory activities. There are reports describing SepA causing destruction of epithelial tissue; however, without cytopathic effect on HEp-2 cells. Also, its cellular target is still unknown. EAEC strains that present SepA protein are associated with cases of diarrhea, but its role in the pathogenicity of EAEC remains unknown. Thus, this study aims to determine the function of this autotransporter toxin in some pathogenic mechanisms of EAEC. (AU)