Pathogenesis of infectious diarrhea: GUT PHYSIOLOGY Part 14

GUT PHYSIOLOGY Part 14S dysenteriae: S dysenteriae causes dysentery, an acute infectious rectocolitis resulting in low volume bloody diarrhea that is often preceded by a watery diarrhea phase. While the precise mechanism of watery diarrhea induction is not entirely clear, in particular the role played by Stx, the pathogenesis of the colitic phase of the infection has been well studied. It is essentially an invasive process, with the chromosomally encoded Stx playing an exacerbating rather than an initiating role, as alluded to above in the context of HC caused by EPEC.
The pioneering, detailed genetic study of Shigella invasion, which became the paradigm for the study of several bacterial invasive systems, revealed the existence of a 220 kb virulence plasmid. This large plasmid encodes a type III system that secretes the products of plasmid Ipa (invasion plasmid antigen) genes encoding IpaA, B, C and D and IcsA; IpaB and C are the major effectors of entry into eukaryotic cells, and IcsA (intra-, intercellular spread) is the principal mediator of intercellular spread between epithelial cells. Recently, strides have been made in elucidating the biological correlates of this complex process, a brief summary of which follows. buy antibiotics online
Initial entry of S dysenteriae into the colonic mucosa is via M cells in FAE, through which they migrate without killing the M cell. Shigellae species are then able to infect intestinal epithelial cells via their basolateral membranes; they do not penetrate via brush borders. Infected epithelial cells are induced to release the inflammatory cytokines interleukin (IL)-8 and tumour necrosis factor-alpha. In addition, Shigella species infect macrophages inducing IpaB-mediated apoptosis and IpaB-mediated release from those macrophages of IL-1P, another potent inflammatory cytokine. The inflammatory response destabilizes epithelial integrity and permeability by the extrusion of PMN, thereby allowing direct access of more Shigella species to the basolateral membranes of epithelial cells. Interaction with PMN results in killing of organisms, with concomitant release of tissue-damaging granules. Once inside epithelial cells, IcsA-medi-ated intercellular spread of Shigella organisms takes place with consequent enlargement of the initial focus of infection.

This entry was posted in Diarrhea and tagged Bibrio cholerae, Clostridium difficile, Diarrhea, Escherichia coli, Shigella dysenteri.