VIOLIN: Vaccine Investigation and Online Information Network

Pathogen Page

Shigella

I. General Information

1. NCBI Taxonomy ID:

2. Disease:

Shigellosis

3. Introduction

Shigellosis is caused by Shigella species. It is an important public health problem, espcially in countries with unsafe water supplies and substandard hygiene. The morbidity and mortality due to shigellosis are especially high among children in these developing countries, causing a cycle of impaired nutrition, recurrent infection, and the retardation of growth. The predominant role of transmission is through faecal-oral contact. Shigellosis is characterized by diarrhoea and/or dysentery with frequent bloody, mucoid stools, tenesmus, and abdominal cramps.
Shigella is an uncapsulated, non-motile Gram negative nonsporulating , facultative anaerobic bacilli. Four species of Shigella are able to cause disease: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. Each of these species are subdivided into serotypes based on their O-specific polysaccharide of the LPS.
A variety of antimicrobial agents are effective for the treatment of shigellosis, but options are becoming limited as a result of global drug resistance. Quinolone was one of the preferred agents for treatment of Shigella in the 1990s. New vaccine development has been hampered by three factors: (i) the ineffectiveness of parenterally injected inactivated whole-cell vaccines which led to the belief that serum antibodies do not confer immunity; (ii) the lack of suitable animal model; (iii) only indirect evidence of immune mechanisms in humans (Niyogi, 2005).

4. Microbial Pathogenesis

Infection is generally limited to the intestinal mucosa and involves a possible enterotoxic or cytoxic diarrhoeal prodrome, cytokine-mediated inflammation of the colon, and necrosis of the colonic epithelium. This inflammation is caused by the invasion of Shigella into the colonic epithelium and the lamina propria. Shigella can enter both M cells and enterocytes, reorganizing the cytoskeleton, beginning with the type II secretion system. The colitis and ulceration of the mucosa result in febrile diarrhoea and/or bloody, mucoid stools (Niyogi, 2005).

Shigella strains produce three distinct enterotoxins:
(i) chromosome encoded shigella enterotoxin 1 (SHET1) which is present in all S. flexneri 2a but rarely found in other shigella serotypes. This toxin is enterotoxic, neurotoxic, and cytoxic, with a structure simlilar to the Shiga-like toxins of enterohaemorrhagic E. Coli infection. The toxin is not essential for virulence, but does contribute to the severity of disease manifestations. Also, this toxin adheres to the small intestine receptors and blocks electrolyte, glucose, and amino acid absorption from the intestinal lumen. The B subunit of this toxin binds host cell glycolipid in the large intestine, A1 domain internalized via receptor-mediated endocytosis and causes irreversible inactivation of the 60S ribosomal subunit, inhibiting protein synthesis, causing cell death, microvasculature damage to the intestine, and haemorrhage.
(ii) shigella enterotoxin 2 (SHET2), which is located on a large plasmid associated with the virulence of shigella. SHET2 was found in many shigella of different serotypes and also in enteroinvasive E. coli.
Inactivation of SHET1 and SHET2 through genetic engineering is used for attenuation of new shigella vaccine candidates.
(iii) phage-born Shiga toxin by S. dysenteriae (Niyogi, 2005).

5. Host Ranges and Animal Models

Humans are the only natural host for Shigella, but NHP have also been used in vaccine trials (Niyogi, 2005).

6. Host Protective Immunity

Wild type Shigella infection induces protective immunity, which develops after repeated exposure during childhood. This immunity is serotype specific (e.g., directed to the LPS O antigen of this organism). Shigella antigen specific antibody response develops early in infection and follows the typical course for anti-LPS antibodies, that is, an IgM response that peaks within weeks of exposure and wanes after 1-2 year (Niyogi, 2005).

Loading Pathogen Genes...

Loading Host Genes...

Loading Vaccines...

Loading References...

Table of Contents