Zinc acquisition via ZnuABC in Yersinia pseudotuberculosis facilitates resistance to oxidative stress

Abstract

Yersinia pseudotuberculosis (Yptb) is a primarily rodent pathogen that also causes gastrointestinal diseases in humans and various animal species worldwide. Zinc uptake is essential for bacterial growth and pathogenicity. In this experiment, we confirmed that the znuABC transcription level in Yptb is regulated by Zn2+ concentration, and then constructed a ΔznuCB mutant. This mutation drastically decreased the survival rate of the ΔznuCB strain under primary oxidative stress (caused by hydrogen peroxide and cumene hydroperoxide) compared to the wild-type strain, and all Yptb strains showed lower resistance to oxidative stress under zinc deprivation caused by znuCB deletion or addition of a chelator. Furthermore, reactive oxygen species (ROS) accumulation was increased in the ΔznuCB strain, which suggested that the wild-type strain acquired Zn2+ by means of the ZnuABC transporter to reduce intracellular ROS levels and, so, prevent oxidative damage to cells. Oral infection showed that znuCB deletion did not have a significant effect on bacterial pathogenicity in mice, indicating the existence of other zinc uptake systems in Yptb. Our results not only suggest the importance of zinc uptake for bacterial growth but also provide insight into the antioxidant function of zinc in Yptb.