Zinc Homeostasis in Brucella ovis Under Zinc Scarcity: Characterization of the ZnuABC Zinc Import System and of a Newly Identified Gene of the Zur Regulon

This is the authors' abstract. We don't add key points for this paper.

The zinc import system ZnuABC is essential for the virulence of smooth (bearing O-polysaccharide chains) zoonotic Brucella species but remains uncharacterized in the non-zoonotic rough (lacking O-chains) species Brucella ovis, the causative agent of a type of ovine brucellosis of veterinary and economic importance. In this study, we constructed a panel of B. ovis mutants for genes of the znuACB locus that were characterized by evaluating growth, gene expression, protein abundance, metal content, and virulence in mice. We identified a ZigA ortholog (uncharacterized in the genus Brucella but linked to zinc homeostasis and histidine metabolism in other bacteria) that belongs to the Zur regulon and is transcriptionally modulated in a zinc-dependent manner as the ZnuABC system. A potential link of B. ovis ZigA with histidine catabolism and a crosstalk between the homeostasis of zinc and other metals have been identified as areas for further exploration. Remarkably, the znuA, zigAznuA and znuACB mutants of B. ovis displayed wild-type virulence in mice, which contrasts with the reported attenuation for the znuA mutant of smooth zoonotic Brucella species sharing a high degree of DNA homology. These results significantly enlarge the knowledge about the metallobiology of the genus Brucella, providing new perspectives for related research.