Unraveling the Role of the Zinc-Dependent Metalloproteinase/HTH-Xre Toxin/Antitoxin (TA) System of in the Oxidative Stress Response: Insights into the Stress Response and Virulence.

Toxin/antitoxin (TA) systems have been scarcely studied in , the causative agent of brucellosis, which is one of the most prevalent zoonotic diseases worldwide. In this study, the roles of a putative type II TA system composed by a Zinc-dependent metalloproteinase (ZnMP) and a transcriptional regulator HTH-Xre were evaluated. The deletion of the open reading frame (ORF) BAB1_0270, coding for ZnMP, used to produce a mutant strain, allowed us to evaluate the survival and gene expression of 2308 under oxidative conditions. Our results showed that the mutant strain exhibited a significantly reduced capacity to survive under hydrogen peroxide-induced oxidative stress. Furthermore, this mutant strain showed a decreased expression of genes coding for catalase (E), alkyl hydroperoxide reductase (C) and transcriptional regulators (R and R-like), as well as genes involved in the general stress response, R and E1, when compared to the wild-type strain. These findings suggest that this type II ZnMP/HTH-Xre TA system is required by to resist oxidative stress. Additionally, previous evidence has demonstrated that this ZnMP also participates in the acidic stress resistance and virulence of 2308. Therefore, we propose a hypothetical regulatory function for this ZnMP/HTH-Xre TA system, providing insight into the stress response and its potential roles in the pathogenesis of .