Shigella flexneri

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A Microbial Biorealm page on the genus Shigella flexneri

Classification

Gram-negative entero-invasive bacterium

Higher order taxa

Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacteriales; Enterobacteriaceae.

Genus and Species

Shigella flexneri

Strains: Shigella flexneri 1a. Shigella flexneri 1b. Shigella flexneri 2a. Shigella flexneri 2a strain 2457T. Shigella flexneri 2a strain 301. Shigella flexneri 3a. Shigella flexneri 3b. Shigella flexneri 5. Shigella flexneri 5 strain 8401. Shigella flexneri 5a. Shigella flexneri 6. Shigella flexneri Y.

Description and significance

Shigella flexneri is a non-motile, non-spore forming, rod-shaped bacterium that is physiologically similar to Shigella dysenteriae, Shigella boydii, and Escherichia coli. It is important because it causes shigellosis, an acute bloody diarrhea. Shigella flexneri is the most common cause of the endemic form of shigellosis, and the endemic form is the cause of most Shigellosis-related deaths. While not much of a problem in developed countries, Shigella flexneri (specifically Shigella flexneri 2a) is a major public health concern in developing countries. Shigella was recognized as the cause of bacillary dysentery in the 1890s by Shiga, hence the genus name (Nato et al.). Shigella flexneri 2a strain 301 was isolated and sequenced by Jin et al. They isolated the bacterium from a shigellosis patient in China in 1984. The chromosomal and plasmid libraries were separately constructed via random shotgun sequencing (Jin et al.).

Genome structure

Shigella flexneri 2a strain 301 has a completely sequenced genome. It consists of a single, 4,607,203 bp circular dsDNA chromosome and a 221,618 bp virulence plasmid (pCP301). The chromosome has 45.8% GC content and 272 genes. The virulence plasmid encodes virulence determinants including invasion plasmid antigens (Ipa) and the Mxi-Spa type III secretion apparatus, but the chromosome also contributes to virulence. Virulence involves a complex regulatory interplay between the chromosome and the virulence plasmid (Jin et al.).

Shigella flexneri's physiological similarity to Escherichia coli could very well have an evolutionary basis. A recent genetic analysis suggests that Shigella may not be a genus because its species may have independent origins from Escherichia coli somewhere between 35,000 and 270,000 years ago (Jin et al.).

Cell structure and metabolism

Lipopolysaccharide (LPS) is found on the surface of Shigella flexneri. It is the repeating sugar portion (O-antigen) of LPS that defines each serotype (Nato et al.). This polysaccharide specificity can be used to target specific serotypes of Shigella (see "Current Research").

Shigella flexneri causes infection via a Type III secretion system. The secretion system acts as a "biological syringe" that injects a protein called Ipa into epithelial cells. Ipa induces the endocytosis of the bacterium and the subsequent lysis of the vacuolar membrane that releases the bacterium into the cytoplasm, where the bacterium proliferates (Clark and Maurelli).

Shigella flexneri is a facultative anaerobe. It makes ATP via aerobic respiration in the presence of oxygen and via fermentation in the absence of oxygen. Although it is closely related to Escherichia coli, Shigella flexneri can be differentiated because it fails to ferment lactose or decarboxylate lysine (Jin et al.).

Ecology

Some strains of Escherichia coli can exert an antagonistic effect on Shigella flexneri. If Shigella flexneri is grown in the digestive tract of a germ-free mouse for 1 day before introducing Escherichia coli, Shigella flexneri disappears within 8 days. However, allowing Shigella flexneri to grow in the mice without Escherichia coli allows for the development of Shigella flexneri resistant to the antagonistic effects of Escherichia coli, but the resistance only occurred in vivo and not in vitro. The Escherichia coli-resistant population emerges without exposure to Escherichia coli, so Escherichia coli-resistance does not appear to be a selective influence in the emergence of the resistant population (Ducluzeau and Raibaud).

Shigella flexneri is prevalent in developing countries because sanitation is poor. The bacterium is found in the feces of infected individuals, so water polluted with feces can act as a route of infection (Huang and Zhou).

Pathology

In humans and other primates, Shigella flexneri causes an acute bloody diarrhea known as shigellosis or bacillary dysentery (Jin et al.). Aside from bloody diarrhea, other symptoms include fever and stomach cramps. The bleeding is due to destruction of the intestines. The bacteria destroy the intestinal epithelium, then continue to break down the intestinal mucosa in the cecum and rectum (Clark and Maurelli). The condition can be fatal if not treated, and early diagnosis is important to effective therapy (Nato et al.). Shigella flexneri is not susceptible to dapsone, but it is susceptible to ampicillin, nalidixic acid, ciprofloxacin, and trimethoprim/sulfamethoxazole (AKA Bactrim or Septra). However, antibiotics should be used only for severe cases since antibiotic resistance is on the rise (Huang and Zhou).

Infection typically occurs via ingestion. Once internalized, Shigella flexneri survives within human hosts by causing apoptosis (programmed cell death) in macrophages while inhibiting apoptosis in epithelial cells. A protein called IpaB activates caspase 1 in macrophages, and the caspase cascade leads to apoptosis (Clark and Maurelli). However, the bacterium uses other mechanisms to inhibit apoptosis in epithelial cells (see "Current Research").

Application to Biotechnology

Shigella flexneri is a bacterial pathogen that is not used for biotechnology.

Current Research

The suppressed immune systems of AIDS patients make them more vulnerable to diarrhea caused by Shigella flexneri and other pathogens. The lack of helper T cells makes AIDS patients susceptible to illness in general, and diarrhea happens to be one of the most common illnesses. However, an intensive handwashing regimen can be used to lower the incidence of diarrhea. There is an inverse relationship among AIDS patients between handwashing frequency and the occurrence of diarrhea (Huang and Zhou).

Shigella flexneri 2a can be detected quickly from stool samples at bedside. The detection test involves a dipstick coated with monoclonal antibodies specific for Shigella flexneri 2a LPS, which includes a repeating, branched pentasaccharide as part of its O-antigen. Strain 2a was selected because it is the strain most associated with endemics. The test can detect low levels of Shigella flexneri within 15 minutes and was shown to have both high specificity and sensitivity (Nato et al.).

Shigella flexneri appears to be able to inhibit apoptosis in epithelial cells. HeLa cells infected with Shigella flexneri resisted apoptosis after exposure to staurosporine, whereas uninfected cells appeared apoptotic. Infected cells had cytochrome c release and activated caspase 9 but no activated caspase 3, suggesting that Shigella flexneri inhibits caspase 3 activation. The bacteria must invade, have a functional type III secretion system, and have a functioning mxiE gene to block apoptosis in epithelial cells. The mxiE gene encodes a transcriptional activator for intracellullar genes, some of which are presumably involved in apoptosis inhibition (Clark and Maurelli).

References

Clark, C. S., and A. T. Maurelli. 2007. "Shigella flexneri Inhibits Staurosporine-Induced Apoptosis in Epithelial Cells." Infection and Immunity, vol. 75, no. 5. (2531-2539)

Ducluzeau, R., and P. Raibaud. 1974. "Interaction between Escherichia coli and Shigella flexneri in the Digestive Tract of "Gnotobiotic" Mice." Infection and Immunity, vol. 9, no. 4 (730-733)

Huang, D. B., and J. Zhou. 2007. "Effect of intensive handwashing in the prevention of diarrhoeal illness among patients with AIDS: a randomized controlled study." Journal of Medical Microbiology, vol. 56, no. 5. (659-663)

Jin, Q., Yuan, Z., Xu, J., Wang, Y., Shen, Y., Lu, W., Wang, J., Liu, H., Yang, J., Yang, F., Zhang, X., Zhang, J., Yang, G., Wu, H., Qu, D., Dong, J., Sun, L., Xue, Y., Zhao, A., Gao, Y., Zhu, J., Kan, B., Ding, K., Chen, S., Cheng, H., Yao ,Z., He, B., Chen, R., Ma, D., Qiang, B., Wen, Y., Hou, Y., and Yu, J. 2002. "Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157." Nucleic Acids Research, vol. 30, no. 20 (4432-4441)

Nato, F., A. Phalipon, L. P. Nguyen, T. T. Diep, P. Sansonetti, and Y. Germani. 2007. "Dipstick for Rapid Diagnosis of Shigella flexneri 2a in Stool." PLoS ONE, vol. 2, no. 4. (e361)

Edited by Roman Fajardo, student of Rachel Larsen and Kit Pogliano at UCSD.

KMG