The YsrS Paralog DygS Has the Capacity To Activate Expression of the Yersinia enterocolitica Ysa Type III Secretion System

Abstract

The Yersinia enterocolitica Ysa type III secretion system (T3SS) is associated with intracellular survival, and, like other characterized T3SSs, it is tightly controlled. Expression of the ysa genes is only detected following growth at low temperatures (26°C) and in high concentrations of sodium chloride (290 mM) in the medium. The YsrSTR phosphorelay (PR) system is required for ysa expression and likely responds to NaCl. During our investigations into the Ysr PR system, we discovered that genes YE3578 and YE3579 are remarkably similar to ysrR and ysrS, respectively, and are probably a consequence of a gene duplication event. The amino acid differences between YE3578 and ysrR are primarily clustered into two short regions. The differences between YE3579 and ysrS are nearly all located in the periplasmic sensing domain; the cytoplasmic domains are 98% identical. We investigated whether these paralogs were capable of activating ysa gene expression. We found that the sensor paralog, named DygS, is capable of compensating for loss of ysrS, but the response regulator paralog, DygR, cannot complement a ysrR gene deletion. In addition, YsrR, but not DygR, interacts with the histidine phosphorelay protein YsrT. Thus, DygS likely activates ysa gene expression in response to a signal other than NaCl and provides an example of a phosphorelay system in which two sensor kinases feed into the same regulatory pathway. IMPORTANCEAll organisms need mechanisms to promote survival in changing environments. Prokaryotic phosphorelay systems are minimally comprised of a histidine kinase (HK) that senses an extracellular stimulus and a response regulator (RR) but can contain three or more proteins. Through gene duplication, a unique hybrid HK was created. We show that, while the hybrid appears to retain all of the phosphorelay functions, it responds to a different signal than the original. Both HKs transmit the signal to the same RR, which activates a promoter that transcribes a set of genes encoding a type III secretion system (T3SS) whose function is not yet evident. The significance of this work lies in finding that two HKs regulate this T3SS, highlighting its importance. Yersinia enterocolitica is a foodborne pathogen known to cause a variety of gastrointestinal disorders, ranging from mild to severe (1). Most healthy individuals only experience fever, vomiting, and diarrhea, lasting just a few days. However, in young children and those with weak or compromised immune systems, Y. enterocolitica can spread systemically, resulting in a 50% mortality rate (2). In addition, postinfection sequelae can be problematic, with the development of reactive arthritis and thyroid disorders (1). More recently, development of inflammatory bowel disease (IBD) has been linked to gastrointestinal infections. While the number of patients developing IBD following Y. enterocolitica infection is comparatively low, the rate is much higher than in patients who were infected with other common enteric pathogens (3, 4). Diagnosis of Y. enterocolitica...

How Salt (NaCl) stress modulates histidine kinase-based signalling systems

“…In EvgS periplasmic sensor region comprising two tandem PBPb (bacterial periplasmic solute-binding protein) domains senses alkali metals, while low pH was perceived by the cytoplasmic linker domain, connecting the transmembrane region and the histidine kinase domain (Eguchi and Utsumi 2014). Similarly to EvgS, Yersinia enterocolitica senses NaCl through YsrS kinase, carrying a related PBP2-type domain (Walker et al 2016).…”