Development of a new guinea-pig model of shigellosis

Barman, Soumik; Saha, Dhira Rani; Ramamurthy, Thandavarayan; Koley, Hemanta

doi:10.1111/j.1574-695x.2011.00810.x

Cited by 20 publications

(22 citation statements)

References 29 publications

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“…Our results demonstrate that mouse jejunum in the Ussing chamber system is as responsive to Shigella toxins as rabbit jejunum. Although several models of shigellosis have been developed, including the nonhuman primate model, the guinea pig keratoconjunctivitis model, and the pulmonary shigellosis model, the models do not adequately measure the watery diarrheal phase of infection [32], [33]. This study is the first to demonstrate secretogenic reactivity in an ex vivo mouse jejunum model to Shigella toxins.…”

Section: Discussionmentioning

confidence: 89%

Chromosomal and Plasmid-Encoded Factors of Shigella flexneri Induce Secretogenic Activity Ex Vivo

et al. 2012

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Shigella flexneri is a Gram-negative, facultative intracellular pathogen that causes millions of cases of watery or bloody diarrhea annually, resulting in significant global mortality. Watery diarrhea is thought to arise in the jejunum, and subsequent bloody diarrhea occurs as a result of invasion of the colonic epithelium. Previous literature has demonstrated that Shigella encodes enterotoxins, both chromosomally and on the 220 kilobase virulence plasmid. The Shigella Enterotoxins 1 and 2 (ShET1 and ShET2) have been shown to increase water accumulation in the rabbit ileal loop model. In addition, these toxins increase the short circuit current in rabbit tissue mounted in Ussing chambers, which is a model for the ion exchange that occurs during watery diarrhea. In this study, we sought to validate the use of mouse jejunum in Ussing chamber as an alternative, more versatile model to study bacterial pathogenesis. In the process, we also identified enterotoxins in addition to ShET1 and ShET2 encoded by S. flexneri. Through analysis of proteins secreted from wildtype bacteria and various deletion mutants, we have identified four factors responsible for enterotoxin activity: ShET1 and Pic, which are encoded on the chromosome; ShET2 (encoded by sen or ospD3), which requires the type-III secretion system for secretion; and SepA, an additional factor encoded on the virulence plasmid. The use of mouse jejunum serves as a reliable and reproducible model to identify the enterotoxins elaborated by enteric bacteria. Moreover, the identification of all Shigella proteins responsible for enterotoxin activity is vital to our understanding of Shigella pathogenicity and to our success in developing safe and effective vaccine candidates.

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Section: Discussionmentioning

confidence: 89%

Chromosomal and Plasmid-Encoded Factors of Shigella flexneri Induce Secretogenic Activity Ex Vivo

et al. 2012

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“…Weight lost was not observed in piglets inoculated with the attenuated Shiga toxin negative strain [63]. Weight loss during S. flexneri 2a infection has also been reported in other animal models of infection [64-66]. …”

Section: Discussionmentioning

confidence: 93%

Impact of Dynasore an Inhibitor of Dynamin II on Shigella flexneri Infection

2013

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Shigella flexneri remains a significant human pathogen due to high morbidity among children < 5 years in developing countries. One of the key features of Shigella infection is the ability of the bacterium to initiate actin tail polymerisation to disseminate into neighbouring cells. Dynamin II is associated with the old pole of the bacteria that is associated with F-actin tail formation. Dynamin II inhibition with dynasore as well as siRNA knockdown significantly reduced Shigella cell to cell spreading in vitro. The ocular mouse Sereny model was used to determine if dynasore could delay the progression of Shigella infection in vivo. While dynasore did not reduce ocular inflammation, it did provide significant protection against weight loss. Therefore dynasore's effects in vivo are unlikely to be related to the inhibition of cell spreading observed in vitro. We found that dynasore decreased S. flexneri-induced HeLa cell death in vitro which may explain the protective effect observed in vivo. These results suggest the administration of dynasore or a similar compound during Shigella infection could be a potential intervention strategy to alleviate disease symptoms.

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“…These strains were obtained from the National Institute of Cholera and Enteric Diseases (NICED) culture collection division. Invasiveness of these strains was confirmed phenotypically by Sereny test, invasion assay in a Caco2 cell line (Mitra et al, 2013) and in a guinea pig colitis model (Barman et al, 2011). The genotypic characterizations of all strains were observed through PCR based methods with the primers for virulence genes (Mitra et al, 2012).…”

Section: Bacterial Strains and Culture Conditionsmentioning

confidence: 99%