1887

Abstract

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, 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 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.

Funding
This study was supported by the:
  • National Institutes of Health (Award RC1GM091238)
  • Florida Department of Health Biomedical Research Programs (Award 3KB04)
  • National Science Foundation of China (Award 31170128)
  • National Basic Research Program of China (Award 973 Program, 2012CB518700)
  • Basic Science Research Program (Award 2010-0009047)
  • the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology
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/content/journal/micro/10.1099/mic.0.078139-0
2014-07-01
2021-08-02
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