Enteric infection meets intestinal function: how bacterial pathogens cause diarrhoea
Key Points Great advances have been made in understanding the adherence and virulence factors of enteric pathogens, the basic physiology of the intestine and the role of innate immunity in health and disease. This Review focuses on the primary links between enteric bacterial pathogens and diarrhoea....
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Veröffentlicht in: | Nature reviews. Microbiology 2009-02, Vol.7 (2), p.110-119 |
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Great advances have been made in understanding the adherence and virulence factors of enteric pathogens, the basic physiology of the intestine and the role of innate immunity in health and disease. This Review focuses on the primary links between enteric bacterial pathogens and diarrhoea.
Whereas the effect of cholera toxin on cystic fibrosis transmembrane regulator-dependent chloride and fluid secretion is well established, recent studies have uncovered the mechanisms by which the toxin finds its way from the bacterium into the host cell cytosol.
Bacteria that do not typically produce toxins can also alter various ion transporters on intestinal epithelial cells. The majority of work in this regard pertains to enteropathogenic
Escherichia coli.
The effect of enteropathogenic
E. coli
effector molecules (secreted through its type III secretion system) on specific epithelial cell ion transporters is discussed.
Tight junctions are composed of several proteins that together form a regulatable paracellular barrier to fluid and electrolytes, and also facilitate vectorial transport by maintaining distinction between the apical and basolateral sides of the epithelial monolayer (fence function). Several enteric pathogens disrupt tight junctions, and perturb barrier and fence functions. The relationship between these effects and diarrhoea is explored.
Intestinal pathogens encounter, and often manipulate, the innate immune system. This is an active area of investigation and is providing fundamental insights about the mammalian innate immune system. The relationship between bacterium-induced inflammation and diarrhoea is not clear; nevertheless, some speculations can be made on the basis of recent studies.
The ancient art of using bacteria to fight bacteria, namely the use of probiotic organisms for therapeutic interventions, is being actively explored. Moreover, advances in related areas are allowing the exploration of the scientific basis for the beneficial effects of probiotic organisms. Some current Phase III clinical trials are exploring the applicability of these approaches to combat diarrhoeal illnesses worldwide.
Bacterial diarrhoea is caused by toxins that are secreted by a variety of bacterial species. These toxins target different host factors and cause loss of fluid and electrolytes, leading to diarrhoea. In addition, the host innate immune response plays an important part in modulating fluid loss.
Infectious diarrhoea is a significant contributo |
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ISSN: | 1740-1526 1740-1534 |
DOI: | 10.1038/nrmicro2053 |