The Neuroendocrine Stress Hormone Norepinephrine Augments Escherichia coli O157:H7-Induced Enteritis and Adherence in a Bovine Ligated Ileal Loop Model of Infection

Abstract

The role of the neuroendocrine environment in the pathogenesis of enteric bacterial infections is increasingly being recognized. Here we report that norepinephrine augments Escherichia coli O157:H7-induced intestinal inflammatory and secretory responses as well as bacterial adherence to intestinal mucosa in a bovine ligated ileal loop model of infection. Norepinephrine modulation of enteritis and adherence was dependent on the ability of E. coli O157:H7 to form attaching and effacing lesions.Enterohemorrhagic Escherichia coli (EHEC) causes acute gastroenteritis in humans that may be complicated by lifethreatening systemic sequelae depending on serotype-and host-specific factors (35). EHEC strains are defined by their ability to produce one or more Shiga-like toxins and to induce characteristic attaching and effacing (A/E) lesions on intestinal epithelia (33). A/E lesion formation relies on the injection of bacterial effectors via a type III secretion system and is determined by the locus of enterocyte effacement (LEE) (14). The LEE-encoded adhesin intimin is required for the colonization of calves and adult cattle by E. coli O157:H7 (6, 8) and for the colonization of humans by enteropathogenic E. coli (EPEC) (11). Type III secreted proteins also mediate the intestinal colonization of calves by EHEC serotypes O157:H7 and O26:H Ϫ (F. Dziva, P. van Diemen, M. Stevens, and T. Wallis, unpublished data), and EspB is required for the carriage and virulence of EPEC in humans (42).The host factors contributing to the colonization of ruminants and humans by EHEC are poorly understood. Recent studies have suggested that the neuroendocrine environment in the gastrointestinal tract may influence the outcome of infection, since the expression of virulence factors by diarrheagenic E. coli is augmented in vitro by the hormone norepinephrine (NE), which is released by the enteric nervous system under stress (3). NE is taken up by E. coli (23) and stimulates the in vitro expression of the K99 pilus adhesin by enterotoxigenic E. coli (27) as well as growth, iron acquisition, motility, and the expression of Shiga-like toxins and LEE-encoded proteins by EHEC O157:H7 (16,29,30,39). NE also augments the adherence of E. coli O157:H7 to murine cecal explants in vitro (5) and the invasion of the porcine jejunal mucosa (18). NEcontaining neurons innervate all levels of the gastrointestinal tract and terminate in neural plexuses and the mucosa (24). The influence of NE released into the gut on the carriage and virulence of gram-negative bacterial pathogens in vivo has received little attention to date.We have examined the effect of NE on the adherence and enteropathogenicity of E. coli O157:H7 in a bovine ligated ileal loop model of infection. This model permits the simultaneous testing of different treatments in discrete segments of the midileum for their effect on bacterial adherence and the induction of intestinal inflammatory and secretory responses (40). All animal procedures were performed in accordance with the Animals (Scientific P...

Stress and microbial endocrinology: prospects for ruminant nutrition

“…NA was shown to enhance expression of Microbial endocrinology and ruminants the K99 pilus adhesin of enterotoxigenic E. coli and type 1 fimbriae of commensal E. coli (Hendrickson et al, 1999). Later work by Vlisidou and co-workers examined the effect of NA on the adherence and enteropathogenicity of E. coli O157:H7 using a bovine ligated ileal loop model of infection (Vlisidou et al, 2004). NA was found to enhance E. coli O157:H7-induced intestinal cell inflammatory and secretory responses, and significantly increased adherence of the Figure 2 Model showing how enteropathogenic bacteria might behave in the gastrointestinal (GI) tract of a stressed bovine host.…”

“…The increasing numbers of pathogens, and possibly also endogenous gut bacteria (Lyte and Bailey, 1997;Bailey et al, 2006 and, could affect gut integrity leading to bacterial translocation (iii) either to the mesenteric lymphatic tissue or, in a worst-case scenario, directly into the systemic circulation, where even commensal bacteria could lead to sepsis and multiple organ failure. Previous exposure to NA might also cause increased expression of E. coli virulence genes, leading to increased attachment of the pathogen to the gut mucosa, either through non-intimate attachments (Chen et al, 2006) (iv) or through espA-or locus of enterocyte effacement (LEE)-dependent intimate attachment (Vlisidou et al, 2004;Kendall et al, 2007) (v and vi), causing the attaching and effacing lesions characteristic of enteropathogenic and enterohaemorrhagic E. coli (note that this figure was adapted with permission from Freestone et al 2008). bacteria to the intestinal mucosa. In the Vlisidou et al study, NA modulation of enteritis and adherence was dependent on the ability of the E. coli O157:H7 to form attaching and effacing lesions.…”

Role of Intimin-Tir Interactions and the Tir-Cytoskeleton Coupling Protein in the Colonization of Calves and Lambs by Escherichia coli O157:H7

“…However, we recently reported that 85-170 Nal r can be induced to form extensive A/E lesions on the ileal mucosa of 28-day-old conventional calves in the presence of the neuroendocrine hormone norepinephrine (NE) (49). Following these observations, we used the bovine ligated intestinal loop assay to assess the role of TccP in the ability of EHEC O157:H7 to adhere to ileal mucosa and to induce the formation of A/E lesions in the presence of 5 mM NE.…”

Genome-Wide Transposon Mutagenesis Identifies a Role for Host Neuroendocrine Stress Hormones in Regulating the Expression of Virulence Genes inSalmonella

“…Stress triggers an increase in plasma epinephrine levels (31), and plasma levels of epinephrine and norepinephrine have been reported to increase with patients suffering from postoperative sepsis compared to patients with no complications (32). Administration of norepinephrine and epinephrine to otherwise healthy subjects increases the severity of bacterial infections, including Clostridium perfringens in humans and enterohemorrhagic Escherichia coli (EHEC) in calves (42,63,65). Treatment with norepinephrine also increases the virulence of Salmonella enterica serovar Enteritidis in chicks and Salmonella enterica serovar Typhimurium in mice, with a substantial increase in bacterial numbers recovered from the cecum and liver in both cases (47,65).…”