Klebsiella pneumoniae is a Gram-negative bacterial pathogen, most commonly associated with respiratory and nosocomial infections. It is also an ESKAPE pathogen and a WHO priority pathogen due to high levels of antibiotic resistance. As such, alternate methods for control of pathogenicity are highly desirable. Zinc is a first-row transition metal ion that is essential for numerous biological functions in all forms of life. Nevertheless, it can exert significant toxicity in excess. Accordingly, bacterial cells tightly regulate cytoplasmic zinc abundance to ensure sufficiency for physiological functions and preventing excess accumulation that can lead to protein mismetallation. It logically follows that interference with these pathways may provide novel avenues for antimicrobial therapies.
Zinc homeostasis remains poorly defined in Klebsiella pneumoniae. However, model Enterobacteriacae, namely Escherichia coli and Salmonella enterica, have been extensively studied with respect to zinc homeostasis. In these bacteria, zinc homeostasis is mediated by a number of proteins, including the zinc responsive regulator Zur, the Znu and Zup importer systems and Znt, Zit and Mdt exporter systems. Here, we report an investigation into the zinc homeostatic mechanisms of K. pneumoniae strain AJ218. This was addressed by examining phenotypic growth and how it was impacted in zinc restricted and replete conditions. Transcriptional analyses identified genes associated with zinc starvation and intoxication. We then generated mutant strains deficient in the putative zur, znuA and zntA genes and assessed the impact on resistance to zinc stress. These data provide a foundation for further studies of zinc homeostasis and its role in the physiology of this priority bacterial pathogen.