Open AccessPseudomonas aeruginosa injects NDK into host cells through a type III secretion system
Author(s) -
Dennis Kyle Neeld,
Yongxin Jin,
Candace Bichsel,
Jinghua Jia,
Jun Guo,
Fang Bai,
Weihui Wu,
Un-Hwan Ha,
Naohiro Terada,
Shouguang Jin
Publication year - 2014
Publication title -
microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 179
eISSN - 1465-2080
pISSN - 1350-0872
DOI - 10.1099/mic.0.078139-0
Subject(s) - effector , secretion , biology , cytotoxic t cell , pseudomonas aeruginosa , type three secretion system , nucleoside diphosphate kinase , microbiology and biotechnology , cytotoxicity , intracellular , kinase , in vitro , bacteria , virulence , biochemistry , gene , genetics
Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen possessing a type III secretion system (T3SS) which injects toxic effector proteins into mammalian host cells. In previous studies, P. aeruginosa strains lacking all of the known type III effectors were shown to cause cytotoxicity upon prolonged infection time. In this study, we report the identification of a new cytotoxin, nucleoside diphosphate kinase (NDK), which is injected into eukaryotic cells in a T3SS-dependent manner. Injection of NDK is inhibited by the presence of previously known effectors of the T3SS, with an effectorless strain injecting the highest amount, suggesting active competition with the known T3SS effectors. NDK is shown to cause a cytotoxic response when expressed in eukaryotic cells, and P. aeruginosa strains harbouring NDK also show a greater toxicity than strains lacking it. Interestingly, the cytotoxic effect of intracellular NDK is independent of its kinase activity. In previous studies, NDK was shown to be secreted into culture supernatants via a type I secretion system and cause cytotoxicity in a kinase-dependent manner. Therefore, the current study highlights an alternative route of NDK secretion as well as two different cytotoxic mechanisms of NDK, depending on the extra- or intra-cellular location of the protein.