Abstract
Shigella flexneri is an important foodborne bacterial pathogen with infectious dose as low as 10–100 cells. SlyA, a transcriptional regulator of the MarR family, has been shown to regulate virulence in a closely related bacterial pathogen, Salmonella Typhimurium. However, the regulatory role of SlyA in S. flexneri is less understood. Here we applied unbiased proteomic profiling to define the SlyA regulon in S. flexneri. We found that the genetic ablation of slyA led to the alteration of 18 bacterial proteins among over 1400 identifications. Intriguingly, most down-regulated proteins (whose expression is SlyA-dependent) were associated with bacterial acid resistance such as the glutamate decarboxylation system. We further demonstrated that SlyA directly regulates the expression of GadA, a glutamate decarboxylase, by binding to the promotor region of its coding gene. Importantly, overexpression of GadA was able to rescue the survival defect of the ΔslyA mutant under acid stress. Therefore, our study highlights a major role of SlyA in controlling S. flexneri acid resistance and provides a molecular mechanism underlying such regulation as well.
Highlights
The bacterium Shigella flexneri (S. flexneri) is an intracellular pathogen that causes gut infection resulting in watery diarrhea or bacillary dysentery (Kotloff et al, 1999)
MurI is a racemase catalyzing the interconversion of L-glutamate to D-glutamate, and it is related to the GadAB-mediated bacterial antiacid system
The MarR/SlyA family of transcriptional regulators has been identified in a variety of Gram-negative bacteria
Summary
The bacterium Shigella flexneri (S. flexneri) is an intracellular pathogen that causes gut infection resulting in watery diarrhea or bacillary dysentery (Kotloff et al, 1999). A major virulence determinant of S. flexneri is a large 230-kb plasmid that encodes the bacterial type III secretion system (T3SS) (Mattock and Blocker, 2017). Working as a molecular syringe, the T3SS is able to translocate an extensive repertoire of effector proteins into host cells, promoting initial bacterial internalization as well as intracellular replication. S. flexneri infection of the gastrointestinal (GI) tract requires successful passage and survival through the highly acidic stomach. A rather striking feature of this bacterium is its extremely low infectious dose of as few as 10–100 bacterial cells. Bacterial acid resistance, in addition to its T3SS, constitutes another critical virulence determinant in Shigella spp
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
