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Pathogenic bacteria could adjust gene expression to enable their survival in the distinct host environment. However, the mechanism by which bacteria adapt to the host environment is not well described. In this study, we demonstrated that nucleoside diphosphate kinase (Ndk) of  Pseudomonas aeruginosa  is critical for adjusting the bacterial virulence determinants during infection.  Ndk  expression was down-regulated in the pulmonary alveoli of a mouse model of acute pneumonia. Knockout of  ndk  up-regulated transcription factor ExsA-mediated T3S regulon expression and decreased exoproduct-related gene expression through the inhibition of the quorum sensing hierarchy. Moreover,  in vitro  and  in vivo  studies demonstrated that the  ndk  mutant exhibits enhanced cytotoxicity and host pathogenicity by increasing T3SS proteins. Taken together, our data reveal that  ndk  is a critical novel host-responsive gene required for coordinating  P. aeruginosa  virulence upon acute infection.

Ndk, a novel host-responsive regulator, negatively regulates bacterial virulence through quorum sensing in Pseudomonas aeruginosa