The Role of Escherichia coli Shiga Toxins in STEC Colonization of Cattle

Abstract

Many cattle are persistently colonized with Shiga toxin-producing Escherichia coli (STEC) and represent a major source of human infections with human-pathogenic STEC strains (syn. enterohemorrhagic E. coli (EHEC)). Intervention strategies most effectively protecting humans best aim at the limitation of bovine STEC shedding. Mechanisms enabling STEC to persist in cattle are only partialy understood. Cattle were long believed to resist the detrimental effects of Shiga toxins (Stxs), potent cytotoxins acting as principal virulence factors in the pathogenesis of human EHEC-associated diseases. However, work by different groups, summarized in this review, has provided substantial evidence that different types of target cells for Stxs exist in cattle. Peripheral and intestinal lymphocytes express the Stx receptor globotriaosylceramide (Gb3syn. CD77) in vitro and in vivo in an activation-dependent fashion with Stx-binding isoforms expressed predominantly at early stages of the activation process. Subpopulations of colonic epithelial cells and macrophage-like cells, residing in the bovine mucosa in proximity to STEC colonies, are also targeted by Stxs. STEC-inoculated calves are depressed in mounting appropriate cellular immune responses which can be overcome by vaccination of the animals against Stxs early in life before encountering STEC. Considering Stx target cells and the resulting effects of Stxs in cattle, which significantly differ from effects implicated in human disease, may open promising opportunities to improve existing yet insufficient measures to limit STEC carriage and shedding by the principal reservoir host.

Primary Human Renal Proximal Tubular Epithelial Cells (pHRPTEpiCs): Shiga Toxin (Stx) Glycosphingolipid Receptors, Stx Susceptibility, and Interaction with Membrane Microdomains

“…HUS is the leading cause of acute kidney injury in children [ 7 ] comprising of thrombocytopenia, microangiopathic hemolytic anemia, and renal failure [ 8 ]. Ruminant animals are deemed to serve as a critical environmental reservoir of STEC [ 9 , 10 ]. The rapid detection of STEC at genetic and phenotypic level enables appropriate monitoring, assessment of the relative virulence of the strains, and treatment of STEC infections [ 11 , 12 ].…”

Primary Human Colon Epithelial Cells (pHCoEpiCs) Do Express the Shiga Toxin (Stx) Receptor Glycosphingolipids Gb3Cer and Gb4Cer and Are Largely Refractory but Not Resistant towards Stx

“…Cattle are a major reservoir of human-pathogenic STEC strains, which can persistently colonize the gut representing a major source of human infections [ 53 ]. Colonization of cattle occurs predominantly in the large intestine, where the pathogens may especially target epithelial cells in the terminal rectum [ 54 ].…”

First Isolation and Molecular Characterization of blaCTX-M-121-Producing Escherichia coli O157:H7 From Cattle in Xinjiang, China

“…E. coli O157:H7 has been reportedly detected in healthy cattle worldwide ( 7 ). The infected, asymptomatic cattle irregularly excrete E. coli O157:H7, resulting in contaminating food and water in the environment, as well as infecting humans and other animals ( 8 ). Cattle are recognized major reservoir and source of E. coli O157:H7.…”