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.
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Univ S Alabama, Coll Med, Dept Microbiol & Immunol, Mobile, AL 36608 USA
Univ S Alabama, Coll Med, Ctr Lung Biol, Mobile, AL 36608 USA
Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USAUniv S Alabama, Coll Med, Dept Microbiol & Immunol, Mobile, AL 36608 USA
Hardy, Kierra S.
Tessmer, Maxx H.
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Univ Washington, Dept Chem, Seattle, WA 98195 USAUniv S Alabama, Coll Med, Dept Microbiol & Immunol, Mobile, AL 36608 USA
Tessmer, Maxx H.
Frank, Dara W.
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Med Coll Wisconsin, Dept Microbiol & Immunol, Milwaukee, WI 53226 USAUniv S Alabama, Coll Med, Dept Microbiol & Immunol, Mobile, AL 36608 USA
Frank, Dara W.
Audia, Jonathon P.
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Univ S Alabama, Coll Med, Dept Microbiol & Immunol, Mobile, AL 36608 USA
Univ S Alabama, Coll Med, Ctr Lung Biol, Mobile, AL 36608 USAUniv S Alabama, Coll Med, Dept Microbiol & Immunol, Mobile, AL 36608 USA
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Nankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R China
Chen, Hao
Gong, Xuetao
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Nankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R China
Gong, Xuetao
Fan, Zheng
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Nankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R China
Fan, Zheng
Xia, Yushan
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Nankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R China
Xia, Yushan
Jin, Yongxin
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Nankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R China
Jin, Yongxin
Bai, Fang
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Nankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R China
Bai, Fang
Cheng, Zhihui
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Nankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R China
Cheng, Zhihui
Pan, Xiaolei
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Nankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R China
Pan, Xiaolei
Wu, Weihui
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Nankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Microbiol, State Key Lab Med Chem Biol, Tianjin, Peoples R China
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Nankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R China
Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Dept Mol Genet, Groningen, NetherlandsNankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R China
Xia, Yushan
Xu, Congjuan
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Nankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R China
Xu, Congjuan
Wang, Dan
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Nankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R China
Wang, Dan
Weng, Yuding
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Nankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R China
Weng, Yuding
Jin, Yongxin
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Nankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R China
Jin, Yongxin
Bai, Fang
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Nankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R China
Bai, Fang
Cheng, Zhihui
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Nankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R China
Cheng, Zhihui
Kuipers, Oscar P.
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Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Dept Mol Genet, Groningen, NetherlandsNankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R China
Kuipers, Oscar P.
Wu, Weihui
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Nankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R ChinaNankai Univ, Coll Life Sci, Minist Educ,Dept Microbiol, State Key Lab Med Chem Biol,Key Lab Mol Microbiol, Tianjin, Peoples R China