Abstract
Type VI secretion systems (T6SSs) are widespread multi-component machineries that translocate effectors into either eukaryotic or prokaryotic cells, for virulence or for interbacterial competition. Herein, we report that the T6SS-4 from Yersinia pseudotuberculosis displays an unexpected function in the transportation of Zn2+ to combat diverse stresses and host immunity. Environmental insults such as oxidative stress induce the expression of T6SS-4 via OxyR, the transcriptional factor that also regulates many oxidative response genes. Zinc transportation is achieved by T6SS-4-mediated translocation of a novel Zn2+-binding protein substrate YezP (YPK_3549), which has the capacity to rescue the sensitivity to oxidative stress exhibited by T6SS-4 mutants when added to extracellular milieu. Disruption of the classic zinc transporter ZnuABC together with T6SS-4 or yezP results in mutants that almost completely lost virulence against mice, further highlighting the importance of T6SS-4 in resistance to host immunity. These results assigned an unconventional role to T6SSs, which will lay the foundation for studying novel mechanisms of metal ion uptake by bacteria and the role of this process in their resistance to host immunity and survival in harmful environments.
Highlights
Specialized protein secretion systems are essential for many bacteria to survive in interactions with their hosts or within specific environmental niches
This study reveals that the T6SS-4 of Yersinia pseudotuberculosis (Yptb) functions to import Zn2+ from the environment to mitigate the detrimental effects such as hydroxyl radicals induced by diverse stresses
Our results reveal a novel role for type VI secretion system, which is important in the study of the mechanism of metal ion acquisition by bacteria and the role of this process in bacterial pathogenesis and survival in detrimental environments
Summary
Specialized protein secretion systems are essential for many bacteria to survive in interactions with their hosts or within specific environmental niches. Type VI secretion system (T6SS) is a complex macromolecular apparatus found in more than 25% of sequenced Gram-negative bacteria genomes, ranging from pathogens to environmental species [1]. Deletion of the T6SS in Helicobacter hepaticus led to mutants that adhere and enter epithelial cell at high efficiencies than wild-type bacteria [5]. In these scenarios, effectors, the T6SS apparatus or its components may stimulate the host immune response to suppress the virulence of wild-type bacteria
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