Cd(II), Pb(II), and Zn(II) ions regulate expression of the metal‐transporting P‐type ATPase ZntA in Escherichia coli Original paper

What was studied?

This study investigates the regulation of the zntA gene in Escherichia coli, which encodes a P-type ATPase that exports toxic metals like Cd(II), Pb(II), and Zn(II) from the cell. Specifically, the research examines how the zntA promoter is activated by the presence of these metal ions, with a particular focus on Cd(II) and Pb(II), which were found to be the most effective inducers of zntA expression. The regulation of zntA is mediated by ZntR, a transcriptional regulator from the MerR family, which facilitates the activation of the gene in response to metal exposure. This study clarifies the role of ZntR in mediating the metal-dependent activation of the zntA transporter and extends previous knowledge on how bacteria respond to metal stress.

Who was studied?

The study centers on Escherichia coli (E. coli) strains, including RK4353, which is used as the wild-type model, and various mutants, such as RKP2910, which carries a single-copy fusion of the zntA promoter with the lacZ reporter gene. Additionally, strains with mutations in the zntA or zntR genes were used to study the specific role of the zntA transporter and the ZntR regulator in response to metal ions like Cd(II), Pb(II), and Zn(II). The study also investigates the effects of metal exposure in defined media, including MOPS minimal medium, which is used to assess the induction of zntA expression under controlled conditions.

Most important findings

The key finding of the study is that Cd(II) and Pb(II), not just Zn(II), are significant inducers of the zntA gene expression in E. coli. Cd(II) was found to be the most effective inducer, triggering a 44-fold induction, while Pb(II) also caused a 3.8-fold induction of the zntA promoter. These inductions were mediated by the ZntR regulator, which binds to the zntA promoter and activates its transcription in response to metal exposure. The study also observed that the zntA mutant strain exhibited higher basal levels of zntA expression than the wild-type strain in the absence of metals, suggesting that metal homeostasis through zntA is tightly regulated even under basal conditions. Furthermore, the study found that other metals like Hg(II) and Ni(II) also induced zntA, but Cd(II) and Pb(II) were much more effective, highlighting their role in ZntA-mediated metal export.

Key implications

The findings underscore the significance of ZntA in protecting E. coli from metal toxicity by exporting not only Zn(II) but also Cd(II) and Pb(II). This mechanism has broader implications for understanding bacterial resistance to environmental metals, especially in settings where exposure to toxic metals like lead and cadmium is high. The ZntR-mediated regulation of zntA expression offers insights into how bacteria adapt to metal stress and could inform the design of bioremediation strategies for contaminated environments. Moreover, understanding how ZntR mediates metal ion-specific regulation could be leveraged for therapeutic interventions to mitigate metal poisoning in clinical settings, as it suggests potential avenues for targeting bacterial metal efflux pumps to control bacterial growth and virulence in environments exposed to toxic metals.