About Shigella

General information:
Gram-negative enteric bacilli, closely related to Escherichia.
Four species: S. dysenteriae, S. flexneri, S. boydii and S. sonnei.
Well-studied example of a facultative intracellular pathogen.
Invasion site: colonic and rectal epithelium.
The initial entry route is M cells in the follicle-associated epithelium (FAE) that overlies the mucosa-associated lymph nodes.
Entry into polarized epithelial cells occurs most efficiently from the basolateral side (Salmonella and EPEC/Shiga toxin producing E. coli are able to interact with host cells from the apical side).
Mode of entry: trigger mechanism.
Shigella, Listeria and Rickettsia are the only three bacterial genera found so far that are able to escape from the phagocytic vacuole and to use cytoplasmic cytoskeletal components to achieve movement and lead to cell-to-cell spread.
Selected genomes:comparative pathogenomics
S. boydii CDC 3083-94, 4615997 bp, NC_010658
S. boydii Sb227, 4519823 bp, NC_007613
S. dysenteriae Sd197, 4369232 bp, NC_007606
S. flexneri 2a str. 2457T, 4599354 bp, NC_004741
S. flexneri 2a str. 301, 4607203 bp, NC_004337
S. flexneri 5 str. 8401, 4574284 bp, NC_008258
S. sonnei Ss046, 4825265 bp, NC_007384
S. boydii CDC 3083-94 pBS512_211, 210919 bp, NC_010660
S. boydii Sb227 pSB4_227, 126697 bp, NC_007608
S. dysenteriae Sd197 pSD1_197, 182726 bp, NC_007607
S. flexneri 2a str. 301 pCP301, 221618 bp, NC_004851
S. flexneri 5a str. M90T pWR501, 221851 bp, NC_002698
S. sonnei Ss046 pSS_046, 214396 bp, NC_007385
Related publications:
Venkatesan MM, et al., 2001. Complete DNA sequence and analysis of the large virulence plasmid of Shigella flexneri Infect. Immun. 69(5):3271-3285.
Jin Q, et al., 2002. Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157. Nucleic Acids Res. 30(20):4432-4441.
Wei J, et al., 2003. Complete genome sequence and comparative genomics of Shigella flexneri serotype 2a strain 2457T. Infect. Immun. 71(5):2775-2786.
Jiang Y, et al., 2005. The complete sequence and analysis of the large virulence plasmid pSS of Shigella sonnei. Plasmid 54(2):149-159.
Yang F, et al., 2005. Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery. Nucleic Acids Res. 33(19):6445-6458.
Nie H, et al., 2006. Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a. BMC Genomics 7:173.
Schema of Shigella invasion strategies (Reproduced from: Sansonetti PJ, 2001. Rupture, invasion and inflammatory destruction of the intestinal barrier by Shigella, making sense of prokaryote-eukaryote cross-talks. FEMS Microbiol. Rev. 25(1):3-14.).

Major virulence factors in Shigella:
Effector delivery system
Pic (Protein involved in intestinal colonization)
SigA (Shigella IgA-like protease homology)
T2SS (Type II secretion system) - S. dysenteriae
T6SS (Type VI secretion system) - S. sonnei
TTSS (Type III secretion system)
TTSS secreted effectors
IcsA (VirG) (Ics for intercellular spread)
ShET1 (Shigella enterotoxin 1)
ShET2 (Shigella enterotoxin 2)
Shiga toxin - S. dysenteriae serotype 1 only
IcsP (SopA)
Immune modulation
Nutritional/Metabolic factor
Shu - S. dysenteriae

Genomic location of virulence-related genes in Shigella:

M cells
Specialized cells devoid of brush border which belong to the follicle-associated epithelium(FEA) that covers the lymph nodes associated with the mucosa. It spares the microbe the need to dissolve the mucus, resist intestinal peristaltism, invade epithelial cells through their apical brush border, or penetrate between cells by opening their tight junctions;The major Gram-negative enteroinvasive pathogens, Shigella, Salmonella, and Yersinia, primarily use the FAE as their entry route.
trigger mechanism
Contact between bacteria and cells results in a dramatic response at the cell surface and bacterial uptake via membrane ruffles, a process resembling macropinocytosis. This mode of entry into non-professional phagocytes is empolyed by Salmonella and Shigella

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