Discovery
The species was named after the American physician Simon Flexner; the genus Shigella is named after Japanese physicianCharacterization
Morphology
''Shigella flexneri'' is a rod shaped, nonflagellar bacterium that relies on actin-based motility. It produces the protein actin in a swift and continuous fashion to propel itself forward within and between the host’s cells. This bacterium is gram-negative, non-spore forming ''Shigella'' from serogroup B. There are 6 serotypes within this serogroup.Serotype
''Shigella flexneri'' belongs to group B (i.e. agglutinate with B antisera) which further subclassified by six type-specific and four group-specific antisera. Until now at least 23 different subserotypes have been identified and reported. PCR based molecular serotyping technique are now available targeting wzx1-5 (All except serotype 6) and gtr genes or wzx6 (Only serotype 6).Invasion
''Shigella flexneri'' is an intracellular bacterium that infects the epithelial lining of the mammalian intestinal tract. This bacterium is acid tolerant and can survive conditions of pH 2. Thus, it is able to enter the mouth of its host and survive passage through the stomach to the colon. Once inside of the colon, ''S. flexneri'' can penetrate the epithelium in three ways: 1) The bacterium can alter the tight junctions between the epithelial cells, allowing it to cross into the sub-mucosa. 2) It can penetrate the highly endocytic M cells that are dispersed in the epithelial layer and cross into the sub-mucosa. 3) After reaching the sub-mucosa, the bacteria can be phagocytosed by macrophages and induce apoptosis, cell death. This releases cytokines that recruit polymorphonuclear cells (PMN) to the sub-mucosa. ''S. flexneri'' still in the lumen of the colon traverse the epithelial lining as the PMNs cross into the infected area. The influx of PMN cells across the epithelial layer in response to Shigella disrupts the integrity of the epithelium allowing lumenal bacteria to cross into the sub-mucosa in an M-cell independent mechanism. ''S. flexneri'' uses these three methods to reach the sub-mucosa to penetrate the epilithelial cells from the basolateral side. The bacterium has four known invasion plasmid antigens: IpaA, IpaB, IpaC, and IpaD. When ''S. flexneri'' makes contact with the basolateral side of an epithelial cell, IpaC and IpaB are fused together to make a pore in the epithelial cell membrane. It then uses a type-III secretion system (T3SS) to insert the other Ipa proteins into the cytoplasm of the epithelial cell. ''S. flexneri'' can pass to neighboring epithelial cells by using its own outer membrane protein, IcsA, to activate the host's actin assembly machinery. The IcsA protein is first localized to one pole of the bacterium where it will then bind with the host's protein, Neural Wiskott-Aldrich Syndrome Protein (N-WASP). This IcsA/N-WASP complex then activates the Actin-related protein (Arp) 2/3 Complex. Arp 2/3 Complex is the protein responsible for rapidly initiating actin polymerization and propelling the bacteria forward. When ''S. flexneri'' reaches the adjoining membrane, it creates a protrusion into the neighboring cell's cytoplasm. The bacteria becomes surrounded by two layers of cellular membrane. It then uses another IpaBC complex to make a pore and enter the next cell. VacJ is a protein that is also needed by ''S. flexneri'' to exit the protrusion. Its exact function is still being studied but it is known that intercellular spread is greatly impaired without it. Bacterial replication within the epithelial cell is detrimental to the cell but it is proposed that epithelial cell death is largely due to the host’s own inflammatory response.Genetics
The genome of ''S. flexneri'' and ''Escherichia coli'' are nearly indistinguishable at the species level. ''S. flexneri'' has a circular chromosome with 4,599,354 base pairs. It is smaller than that of ''E. coli'' but the genes are similar. ''S. flexneri'' has about 4,084 known genes in the genome. The extensive similarity between ''E. coli'' and ''S. flexneri'' is proposed to be due toMetabolism
''Shigella flexneri'' is a heterotroph. It utilizes the Embden-Meyerhof-Parnas (EMP), Entner-Doudoroff (ED), or pentose phosphate pathway (PPP) to metabolize sugars. The products of these pathways then feed into the Citric Acid Cycle (TCA). ''S. flexneri'' can metabolize glucose and pyruvate. Supplemented pyruvate allows for the most growth and is believed to be the preferred carbon source. Pyruvate could be supplied by the cell's own metabolism or taken from the host cell. ''S. flexneri'' is a facultative anaerobe that is able to perform mixed-acid fermentation of pyruvate. ''S. flexneri'' is unable to ferment lactose. This bacterium grows optimally at 37°C but can grow in temperatures as low as 30°C.Small RNA
Ecology
Infectious cycle
''Shigella flexneri'' contains a virulence plasmid that codes for three virulence factors: a type-3 secretion system (T3SS), invasion plasmid antigen proteins (IPA proteins), and IcsA (used for cell-to-cell spread). Upon infection, ''S. flexneri'' injects the host cell cytoplasm with ipa proteins using the T3SS—a needle-and-syringe-like apparatus common to many Gram-negative pathogens. These ipa proteins induce "membrane ruffling" by the host cell. Membrane ruffling creates membrane pockets which capture and engulf the bacteria. Once inside, ''S. flexneri'' uses host cell actin for propulsion to move directly from cell to cell using a cellular mechanism known as paracytophagy, similarly to the bacterial pathogen '' Listeria monocytogenes''. ''Shigella flexneri'' is able to inhibit the acute inflammatory response in the initial stage of infection by using an effector protein, OspI, which is encoded by ''ORF169b'' on the ''Shigella'' large plasmid and secreted by the type III secretion system. It dampens the inflammatory response during bacterial invasion by suppressing the TNF-α-receptor-associated factor 6 ( TRAF6)-mediated signalling pathway. OspI has glutamine deamidase activity, and is able to selectively deaminate glutamine at position 100 in UBC13 toReferences
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