ArsR transcriptional regulator mediated attenuated mechanism by regulating self and outer membrane protein in Brucella

The ArsR family transcriptional regulators are widely distributed in microorganisms, including in the important intracellular pathogen Brucella. ArsR proteins are implicated in numerous biological processes. However, the specific roles of ArsR family members in Brucella remain obscure. Here we show that ArsR3 (BSS2_RS07325) is required for Brucella survival both under stress in vitro conditions and in a murine infection model in vivo. ArsR3 autoregulate its own expression to maintain metal ion homeostasis to benefit bacterial survival. Moreover, ArsR3 also regulates the production of virulence factor outer membrane protein 25D (Omp25D) which is key for the survival of Brucella under stress conditions. Significantly, ArsR3 deletion strain attenuated in a murine infection model in vivo. Altogether, our findings reveal a unique mechanism in which the ArsR family member ArsR3 autoregulates its expression and also modulates Omp25D expression to maintain metal ion homeostasis and virulence in Brucella.