The <i>Klebsiella pneumoniae</i> tellurium resistance gene <i>terC</i> contributes to both tellurite and zinc resistance

<i>Klebsiella pneumoniae</i> is widely recognized as a pathogen responsible for hospital-acquired infections and community-acquired invasive infections. It has rapidly become a significant global public health threat due to the emergence of hypervirulent and multidrug-resistant strains, which have increased the challenges associated with treating life-threatening infections. Tellurium resistance genes are widespread on virulence plasmids in <i>K. pneumoniae</i> isolates. However, the core function of the <i>ter</i> operon (<i>terZABCDEF</i>) in <i>K. pneumoniae</i> remains unclear. In this study, the multidrug-resistant <i>K. pneumoniae</i> P1927 strain was isolated from the sputum of a hospitalized pneumonia patient. The <i>ter</i> operon, along with antimicrobial resistance and virulence genes, was identified on a large hybrid plasmid in <i>K. pneumoniae</i> P1927. We generated a <i>terC</i> deletion mutant and demonstrated that this mutant exhibited reduced virulence in a <i>Galleria mellonella</i> larva infection model. Further physiological functional analysis revealed that <i>terC</i> is not only important for Te(IV) resistance but also for resistance to Zn(II), Mn(II), and phage infection. All genes of the <i>ter</i> operon were highly inducible by Zn(II), which is a stronger inducer than Te(IV), and the <i>terBCDE</i> genes were also induced by Mn(II). Collectively, our study demonstrates novel physiological functions of TerC in Zn(II) resistance and virulence in <i>K. pneumoniae</i>.IMPORTANCE<i>Klebsiella pneumoniae</i> has rapidly become a global threat to public health. Although the <i>ter</i> operon is widely identified in clinical isolates, its physiological function remains unclear. It has been proposed that proteins encoded by the <i>ter</i> operon form a multi-site metal-binding complex, but its exact function is still unknown. TerC, a central component of the tellurium resistance determinant, was previously shown to interact with outer membrane proteins OmpA and KpsD in <i>Escherichia coli</i>, suggesting potential changes in outer membrane structure and properties. Here, we report that TerC confers resistance to Zn(II), Mn(II), and phage infection, and Zn(II) was shown to be a strong inducer of the <i>ter</i> operon. Furthermore, TerC was identified as a novel virulence factor. Taken together, our results expand our understanding of the physiological functions encoded by the <i>ter</i> operon and its role in the virulence of <i>K. pneumoniae</i>, providing deeper insights into the link between heavy metal(loid) resistance determinants and virulence in pathogenic bacteria.