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

Abstract

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.

Characterization of lasR-deficient clinical isolates of Pseudomonas aeruginosa

“…A functional LasR contained the N-terminal autoinducer binding-dimerization domains and a C-terminal DNA binding domain 37 , 38 . To address whether the LasRW60* mutant was, indeed, a loss-of-function variant, the levels of OdDHL produced by LasI in bj13 and bj14 were assessed using reporter assays 39 . While PAO1 generated a high level of OdDHL, neither bj13 nor bj14 produced detectable OdDHL, the observation similar to the PAO1-derived lasR knockout, Δ lasR (Fig.…”

Mechanisms underlying the virulence regulation of new Vibrio alginolyticus ncRNA Vvrr1 with a comparative proteomic analysis

“…Moreover, after infection, ndk released from bacteria are involved in regulating host defense activities, such as cell apoptosis, phagocytosis, and inflammatory responses [56]. In addition, ndk is a critical novel host-responsive gene required for coordinating P. aeruginosa virulence upon acute infection, and its mutant exhibits enhanced cytotoxicity and host pathogenicity by increasing the level of T3SS proteins [57]. The interaction network diagram of Vvrr1 with its potential target genes shows some of the target genes with their virulence function.…”

Quantitative Proteomics of the 2016 WHO Neisseria gonorrhoeae Reference Strains Surveys Vaccine Candidates and Antimicrobial Resistance Determinants

“…In the C fraction, no protein was differentially expressed in all strains, but two cytoplasmic proteins, NGO0597 and NGO0701, were upregulated in all strains except WHO L. NGO0597 is a nucleoside diphosphate kinase (Ndk; 15.4 KDa) involved in DNA and RNA synthesis (143), regulation of gene transcription (144), and peptide chain elongation during translation (145), all processes that are targets for different antimicrobials. NdK is secreted from Pseudomonas aeruginosa (144), M. tuberculosis (146), and Leishmania (147) to modulate interaction with host cells, block phagosome maturation in macrophages (146,148), and promote host cell apoptosis and necrosis (149). It remains to be investigated whether the gonococcal Ndk is secreted during infection and whether it may serve as an anti-virulence or antimicrobial target.…”