Fur-regulated urease contributes to the environmental adaptation of Yersinia pseudotuberculosis.

Abstract

Urease converts urea into ammonia and carbon dioxide, providing a nitrogen and carbon source for microbial growth and serving as an important mechanism for human bacterial pathogens to survive in acidic conditions, which can be regulated by many factors. As a global regulator, the ferric uptake regulator (Fur) regulates a series of genes and pathways involved in many different cellular processes and the virulence of the enteric bacterium Yersinia pseudotuberculosis (Yptb). However, whether Fur regulates the urease activity in Yptb was still unknown. In this study, we found that urease is positively regulated by Fur in response to manganese ions (Mn²⁺), and this regulation by Fur is mediated by specific recognition of the promoter region of urease in Yptb. Furthermore, urease is induced by Mn²⁺ via Fur under low nutrient conditions. Moreover, we provided evidence that urease plays an important role in acid and osmotic stress resistance, biofilm formation, and virulence of Yptb. Our findings provide insights into understanding the regulatory mechanism and multiple functions of urease in Yptb.IMPORTANCEUrease catalyzes the breakdown of urea into ammonia and carbamate, which are widely distributed among bacterial species and play an important role as an important acid resistance system and virulence factor. In most bacterial species, urease expression is tightly regulated in response to environmental cues such as nitrogen status, pH, growth phase, substrate availability, or transcriptional regulators. In this study, we found that urease from Yptb is positively regulated by Fur in response to Mn²⁺ under low nutrient conditions, which functions to combat acid and osmotic stress and enhance biofilm formation, and plays a crucial role in virulence. Importantly, this is the first demonstration of a direct role for Fur and Mn²⁺ in regulating urease expression in Yptb. This study provides a comprehensive understanding of the regulatory mechanisms and functions of urease from Yptb.