Campylobacter jejuni Increases Flagellar Expression and Adhesion of Noninvasive Escherichia coli: Effects on Enterocytic Toll-Like Receptor 4 and CXCL-8 Expression

Abstract

cCampylobacter jejuni is the most common cause of bacterium-induced gastroenteritis, and while typically self-limiting, C. jejuni infections are associated with postinfectious intestinal disorders, including flares in patients with inflammatory bowel disease and postinfectious irritable bowel syndrome (PI-IBS), via mechanisms that remain obscure. Based on the hypothesis that acute campylobacteriosis may cause pathogenic microbiota dysbiosis, we investigated whether C. jejuni may activate dormant virulence genes in noninvasive Escherichia coli and examined the epithelial pathophysiological consequences of these alterations. Microarray and quantitative real-time PCR analyses revealed that E. coli adhesin, flagellum, and hemolysin gene expression were increased when E. coli was exposed to C. jejuni-conditioned medium. Increased development of bacterial flagella upon exposure to live C. jejuni or C. jejuni-conditioned medium was observed under transmission electron microscopy. Atomic force microscopy demonstrated that the forces of bacterial adhesion to colonic T84 enterocytes, and the work required to rupture this adhesion, were significantly increased in E. coli exposed to C. jejuni-conditioned media. Finally, C. jejuni-modified E. coli disrupted TLR4 gene expression and induced proinflammatory CXCL-8 gene expression in colonic enterocytes. Together, these data suggest that exposure to live C. jejuni, and/or to its secretory-excretory products, may activate latent virulence genes in noninvasive E. coli and that these alterations may directly trigger proinflammatory signaling in intestinal epithelia. These observations shed new light on mechanisms that may contribute, at least in part, to postcampylobacteriosis inflammatory disorders. Campylobacter jejuni-induced diarrheal disease (i.e., campylobacteriosis) is a major cause of morbidity worldwide (1). Within the United States alone, more than 800,000 cases of campylobacteriosis are domestically acquired each year, and the annual financial burden of the infection is US$6.9 million (2, 3). Campylobacter is a microaerophilic commensal bacterium of the gastrointestinal tract of food-producing animals such as poultry and cattle, and zoonotic transmission of this pathogen is well established; campylobacteriosis is commonly acquired through ingestion of contaminated water, food, or milk (4, 5). Upon infection in the human host, Campylobacter induces an inflammatory response, which in turn leads to the development of acute symptoms, including diarrhea, abdominal pain, and fever (6, 7). Although Campylobacter infections are generally self-limiting, campylobacteriosis may lead to serious long-term complications via mechanisms that remain obscure. Postinfectious intestinal and extraintestinal sequelae include Guillain-Barré paralysis, reactive arthritis, postinfectious irritable bowel syndrome (PI-IBS), or flares in patients with inflammatory bowel disease (IBD) (8-14). PI-IBS is a functional disorder of the gastrointestinal tract that is characterized by symptoms of abdomina...

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