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

<p><span>The ArsR family transcriptional regulators are widely distributed in microorganisms, including in the important intracellular pathogen <i>Brucella</i>. ArsR proteins are implicated in numerous biological processes. However, the specific roles of ArsR family members in <i>Brucella</i> remain obscure. Here we show that ArsR3 (BSS2_RS07325) is required for <i>Brucella</i> survival both under stress <i>in vitro</i> conditions and in a murine infection model<i> in vivo</i>. 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 <i>Brucella</i> under stress conditions. Significantly, ArsR3 deletion strain attenuated in a murine infection model<i> in vivo</i>. 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 <i>Brucella</i>.</span></p>