Enterohemorrhagic Escherichia coli Pathogenesis and the Host Response

Abstract

Enterohemorrhagic Escherichia coli (EHEC) is a highly pathogenic bacterial strain capable of causing watery or bloody diarrhea, the latter termed hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). HUS is defined as the simultaneous development of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The mechanism by which EHEC bacteria colonize and cause severe colitis, followed by renal failure with activated blood cells, as well as neurological symptoms, involves the interaction of bacterial virulence factors and specific pathogen-associated molecular patterns with host cells as well as the host response. The innate immune host response comprises the release of antimicrobial peptides as well as cytokines and chemokines in addition to activation and/or injury to leukocytes, platelets, and erythrocytes and activation of the complement system. Some of the bacterial interactions with the host may be protective in nature, but, when excessive, contribute to extensive tissue injury, inflammation, and thrombosis, effects that may worsen the clinical outcome of EHEC infection. This article describes aspects of the host response occurring during EHEC infection and their effects on specific organs.

Haemolytic uraemic syndrome

“…Thus, multiple cell types may release potent inflammatory mediators and enzymes. Furthermore, cytokines, chemokines, soluble adhesion molecules, growth factors, cytokine receptors and acute-phase response proteins are elevated in EHEC-associated HUS patients [78,[119][120][121][122][123][124][125][126][127][128][129][130] and may contribute to the progression of renal damage particularly as elevated cytokine levels have been demonstrated in the urine of patients with HUS [121]. The chemokine receptor CXCR4/CXCR7/stromal cell-derived factor 1 pathway is also activated in vivo, and in vitro by Shiga toxin, thus also contributing to renal damage [131].…”

Overview and Historical Perspectives

“…Only decades later, with the evaluation of data obtained from infection of volunteers (17) and subsequently of monkeys (18) with S. dysenteriae type 1, was it clear that production of Stx by the organism exacerbates the severity of the intestinal and systemic lesions in human subjects and increases the intestinal pathology in primate hosts. The ultimate proof of a role for Stx in shigellosis due to Shiga's bacillus was the establishment of a connection between production of this and related toxins with the subsequent development of HUS (see below or references 19 and 20). …”

“…These authors also raised concerns that treatment with antibiotics might lead to excessive bacterial destruction and enhanced absorption of toxin, with an adverse clinical outcome (see reference 58). Additional information on the history of HUS and various proposed pathogenic mechanisms can be found in several reviews (19, 20, 56, 59, 60). …”

“…Risk factors for STEC infections are discussed by Rivas et al in chapter 18 (87). The host response and other aspects of STEC pathogenesis are reviewed by Karpman and Stahl in chapter 19 (20). With the recognition that regulation of EHEC virulence factors can be influenced by commensal intestinal bacteria, the interplay between the microbiota and EHEC can be important, as reviewed by Pifer and Sperandio in chapter 20 (88).…”

Changes in Gene Transcription Induced by Hydrogen Peroxide Treatment of Verotoxin-Producing Escherichia coli O157:H7 and Non-O157 Serotypes on Romaine Lettuce

“…Verotoxin-producing Escherichia coli (VTEC), also referred to as Shiga toxin (Stx)-producing E. coli (STEC), often cause life-threatening diseases, such as hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS) (Croxen et al, 2013; Karpman and Stahl, 2014; Karmali, 2017). Although VTEC serotype O157:H7 is commonly identified in human diseases, non-O157 serogroups have been increasingly associated with serious outbreaks and were recently responsible for more than 50% of STEC illness in U.S. (Luna-Gierke et al, 2014; Parsons et al, 2016; CDC, 2017).…”