| In their life cycle and infection process,bacteria have evolved seven different types of secretion systems,namely type I-Ⅶ secretion system.These secretion systems specifically secrete related substrates and effectors to implement their specific biological functions,which promote bacterial growth and reproduction,environmental adaptability and pathogenicity.Type Ⅵ secretion systems(T6SSs)reported in recent years are widely distributed and are quite complex.T6 SS is mainly involved in the interaction between bacteria and their hosts,the competition between bacteria and the environmental adaptability of bacteria.Study on the environmental adaptability of T6 SS is a new area for bacterial T6 SS research.It is of great significance to reveal the mechanism of environmental adaptability of T6 SS to promote the development of the industrial microbial fermentation,the release of agricultural microbes,and their resistance to host immune systems.Yersinia pseudotuberculosis is a common zoonotic pathogen that can infect wild and domestic animals,as well as humans,sharing high similarity with Y.pestis and Y.enterocolitica in evolution and biochemical characteristics.In Y.pseudotuberculosis,there are four T6 SS gene clusters,which means they possess diversity functions.Previous studies have reported that T6SS4 was involved in bacterial environmental adaptability,however,there’s no in-depth study on the adaptability mechanism.In this study,we chose T6 SS of Y.pseudotuberculosis as the main research object,aiming at revealing the function and regulation mechanism of T6 SS in environmental adaptability.The main results are as follows:1.An ion-binding T6 SS effector,YezP,was found to bind zinc ion and promote the acquisition of zinc ion for bacteria.In insults environment or the process of infecting the host,bacteria are inevitably subjected to various of primary and secondary oxidative stresses,which in turn result in excessive intracellular production of reactive oxygen species(ROS).ROS activates T6SS4 expression via OxyR,and then,the zinc-binding protein YezP will be secreted to extracellular by the highly expressed T6SS4.The extracellular YezP binds zinc ions in the environment,and further promotes the acquisition of zinc ions of bacteria.Moreover,YezP can also compete with iron ions to inhibit the Fenton Reaction and reduce the formation of hydroxyl radicals,a highly toxic ROS species.Ultimately,the serial processes promote the environmental adaptability and pathogenicity of bacteria.2.We revealed the gradient response mechanism of T6SS-YezP-HmuR-ZnuABC system in harsh environment or infecting host:(1)In zinc abundant condition,the bacteria get zinc through the passive diffusion,and the T6SS4 and HmuR systems do not express at this time;(2)The expression of ZnuABC got increased without zinc and oxidative stress in the environment,and T6SS4 and HmuR were partly expressed simultaneously.Zinc ions would be main obtained through the ZnuABC pathways;(3)In the absence of zinc and under oxidative stress condition,the expression of ZnuABC was also associated with the high expression of T6SS4 and HmuR system,and the highly expressed YezP by T6 SS as well.Extracellular Yez P combined with zinc ions help the outer membrane receptor protein HmuR transfer zinc ions into the periplasmic space,and the zinc ions entered the cell through the ZnuABC system,which contribute the bacterial adaptability to harsh environment finally.3.In summary,we revealed two regulatory proteins of T6SS4: ZntR and HpaR.ZntR can regulate T6SS4 expression directly by sensing the concentration of zinc ion,which can cope with bacterial zinc deficiency to promote bacterial environmental adaptability.HpaR responds to organic oxidative stress and directly binds to the T6SS4 promoter to promote the organic oxidative adaptation of bacteria based on T6SS4.The results enrich and improve the environmental regulation of T6SS4 cross-regulation network in Y.pseudotuberculosis. |
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