Insights into the potential functions of nucleoside diphosphate kinases in Waddlia chondrophila encoded by two ndk paralogs

The Chlamydiota phylum consists of obligate intracellular bacteria, including well-known pathogens and emerging environmental species, with diverse host ranges and metabolic capabilities. Among these bacteria, the ndk gene, which encodes nucleoside diphosphate kinase, is present in variable copy numbers. While most chlamydial species carry a single copy of the ndk gene, some species have two copies. In W. chondrophila , both ndk paralogs retain conserved kinase motifs but differ in subcellular localization, suggesting divergent functional roles. WcNdk1 is confined to the inclusion and likely supports nucleotide metabolism, while WcNdk2 localizes to the host nucleus, perinuclear space, and Golgi apparatus, implying involvement in host interaction. Azidothymidine (AZT), a known Ndk inhibitor, was found to impair the growth of W. chondrophila , possibly by targeting WcNdk2 due to its role in host interaction. Our findings shed light on the potential functions of ndk paralogs in W. chondrophila and support a role for WcNdk2 in host manipulation and pathogenesis. This research offers a starting point for deeper functional analyses as genetic manipulation techniques for this organism become more accessible.