For a study, it was determined that shigella was one of the few enteric pathogens that infected colonic epithelia via the basolateral pole. As a result, it had evolved the ability to breach the intestinal epithelial barrier and unleash a slew of effector proteins, allowing bacteria to infiltrate and trigger a severe inflammatory response. On the other hand, Shigella’s strategies for controlling epithelial barrier permeability are unknown. To further describe the early events of host-bacteria interactions, the researchers used both an intestine polarised model and a human ex-vivo model to answer this question. The researchers revealed that secreted Serine Protease A (SepA), a member of the Enterobacteriaceae family of serine protease autotransporters, was responsible for seriously altering the intestinal epithelial barrier. Bacterial passage to the epithelium’s basolateral pole was facilitated due to this disturbance, encouraging the disease pathology’s hallmarks. In addition, SepA was discovered to lower levels of active LIM Kinase 1 (LIMK1), a negative inhibitor of actin-remodeling proteins such as cofilin. Activation of cofilin, a key actin-polymerization factor known to control the opening of tight junctions at the epithelial barrier, was also elevated. The researchers went through the crystal structure of SepA to learn more about how it affects actin dynamics and barrier disruption. SepA’s serine protease activity was discovered to be essential for the regulatory effects on LIMK1 and cofilin, causing the epithelial barrier to be disrupted during infection. Overall, the researchers showed that SepA was required for barrier breakdown and, as a result, Shigella transit to the basolateral pole, where it can efficiently infiltrate the epithelium.
Link:www.tandfonline.com/doi/full/10.1080/19490976.2017.1339006
