The pathogenesis of campylobacter diarrhoea.
thesisposted on 19.11.2015, 08:53 by Paul Howard. Everest
The Pathogenesis of Campylobacter Paul Everest Diarrhoea. Campylobacter jejuni / coli are the most common cause of acute diarrhoeal disease in man. The disease is worldwide, affects all age groups, and is mostly sporadic although common source outbreaks are frequently reported. The organism characteristically causes infection of the small intestine with extension into the colon and rectum, the disease being an acute enterocolitis. Illness may be inflammatory, with mucosal oedema and polymorphonuclear infiltration and blood in the faeces, or non-inflammatory with watery diarrhoea. The pathogenesis of the disease is unknown. Bacterial invasion of intestinal mucosa has been proposed as a mechanism of mucosal inflammation causing tissue damage. Investigation of the enterocyte-like Caco-2 and other epithelial cell lines for the ability of clinically characterised strains to adhere and invade showed that strains from colitic illness exhibited a greater tendency to invade than strains from non-inflammatory illness. Colitis and some non-inflammatory strains were also shown to transcytose from the apical to the basolateral cell membrane. Phosphorylation of mammalian cell proteins (such as ion channels) is important in diarrhoeal illness, mediated by bacterial cells and their secreted toxins. C. jejuni bacterial cells and a secreted toxin in culture supernatants caused phosphorylation of Caco-2 cell proteins, effects that mimic protein kinase C phosphorylation of myosin light chain. Culture supernatants increased intracellular calcium, an effect known to mediate fluid secretion. These effects are independent of the cholera-like toxin that is found in small amounts in culture supernatants. Colitis strains tested in rabbit ileal loops induced similar histological effects to those seen in man, caused fluid secretion, and white cell infiltrate consisting of polymorphonuclear leucocytes and macrophages. Villi were shortened and tissue was oedematous with submucosal bleeding. Tissue damage may prevent effective absorption of fluid and contribute to diarrhoea but biochemical analysis suggests a true secretory component to the diarrhoea. By contrast a non-inflammatory strain showed no histological changes in loops and elicited no fluid secretion. Large amounts of the host derived secretagogue prostaglandin E2 were induced in infected ileal loops and correlated with the tissue white cell infiltrate (along with leukotriene B4). In the absence of a cholera-like toxin produced by the bacteria PGE2 seems to be responsible for the increase in infected tissue cyclic AMP. PGE2 acts by binding to a cellular receptor and activating cell adenylate cyclase resulting in a rise in cAMP. Thus a host inflammatory mediator may contribute to fluid secretion in C. jejuni enterocolitis.