title: 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.
authors.affiliation: Department of Microbiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.|Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Junzhi
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Hu
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xin
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: He
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Halei
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Xiancai
authors.initials: X
authors.lastname: Rao
authors.affiliation: Central Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Kebin
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009701:Nucleoside-Diphosphate Kinase / Q000096:biosynthesis / Q000235:genetics; D011552:Pseudomonas Infections / Q000201:enzymology / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity; D000069296:Type III Secretion Systems / Q000096:biosynthesis / Q000235:genetics; D037521:Virulence Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D000069296:Type III Secretion Systems; D037521:Virulence Factors; D009701:Nucleoside-Diphosphate Kinase