Nucleoside diphosphate kinase (Ndk): A pleiotropic effector manipulating bacterial virulence and adaptive responses.

Nucleoside diphosphate kinase (Ndk) is a housekeeping enzyme that balances cellular nucleoside triphosphate (NTP) pools by catalyzing the reversible transfer of γ-phosphate from NTPs to nucleoside diphosphates (NDPs). In addition to its fundamental role in nucleotide metabolism, Ndk has roles in protein histidine phosphorylation, DNA cleavage/repair, and gene regulation. Recent studies have also revealed that Ndk secreted from bacteria is important in modulating virulence-associated phenotypes including quorum sensing regulation, type III secretion system activation, and virulence factor production. Moreover, after infection, Ndks released from bacteria are involved in regulating host defense activities, such as cell apoptosis, phagocytosis, and inflammatory responses. Given that Ndk exerts a pleiotropic effect on bacterial virulence and bacteria-host interactions, the biological significance of the bacterial Ndks during infection is intriguing. This review will provide a synopsis of the current knowledge regarding the biological properties and roles of Ndks in regulating bacterial virulence and adaptation and will discuss in depth the biological significance of Ndk during bacteria-host interactions.