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Shigellosis: Shigella infection

Shigella causes an estimated 164.7 million cases of diarrhea every year, and 700,000 deaths worldwide. It spreads easily and rapidly from person to person in contaminated food and recreational water, and places like daycare centers. Consumption of raw milk or unpasteurized cheeses remains a risk factor for Shigella infections.

The Pathogen

Shigella was recognized in 1897 by Kiyoshi Shiga as the causative agent of bacillary dysentery, a severe form of Shigellosis (infection with Shigella). It is a gram-negative, rod shaped bacteria, that infects primates but not other mammals. Shigella puts out virluence factors that induce severe inflammation and induces fluid loss in the colon, producing the classic watery diarrhea seen early in infection. Using its Type III Secretion system, the bacterium subverts host cell structure and function to inject its virulence effectors into the host cell, allowing invasion inside where it can grow and ultimately cause destruction of the colon. Effectors are also produced by the bacteria that down-regulate inflammation and the innate immune response, which acts to promote the infection, limit the adaptive immune response, and leave the host partially susceptible to re-infection. The majority of these virulence factors are found on one place "entry region" of a virulence plasmid (small DNA molecule separate from chromosomal DNA that can replicate independently and can be shared from one bacteria to another). However "pathogenicity islands", unstable transferable elements in the chromosomal DNA containing factors that contribute to infection are also found in Shigella strains.



The clinical presentation of a Shigella infection is called Shigellosis. This disease is transmitted through the fecal-oral route, requiring only 10-100 organisms to start an infection. After 1-4 days, the infection has lead to destruction in the colon, leading to diarrhea that can be accompanied by abdominal cramps and fever. Further complications can occur depending on the Shigella species infecting with symptoms such as acute renal failure, low blood platelets, and loss of red blood cells, with a 35% fatality rate. In 2% of cases, post-reactive arthritis occurs, characterized by painful joints, painful urination, and irritation of the eyes.

Shigella Antibiotic Resistance

In the United States, most Shigella is already resistant to the antibiotics ampicillin and trimethoprim/sulfamethoxazole. The first choice of treatment today is ciprofloxacin, but resistance is already increasing globally. Until recently, resistance to ciproflacin in the US was only 2% of Shigella infections, but resistance was found in 90% of samples tested from recent clusters. Ciprofloxacin-resistant Shigella sickened 243 people in 32 US states between 2014-2015. CDC researchers discovered that the illness was repeatedly introduced as sick travelers returned, infecting others in a series of outbreaks around the US.


Pathogens reWritE Rho's rules 

Many bacterial pathogens use a specialized "type III" secretion system to deliver virulence effector proteins into host mammalian cells. Here a new family of effectors are described that directly stimulate host signaling pathways by mimicking activated Ras-like cellular GTPases and targeting the actin cytoskeleton. These results suggest that direct GTPase mimicry may be widely used mechanism in bacteria-host interactions.

Read the Cell Article Here