Study On The Mechanism Of Pseudomonas Citronellae SJTE-3 Tellurite Resistance Protein Tera Affecting Cell Division

Tellurite is a kind of compounds which can effectively inhibit the growth of microorganisms at low concentration.Tellurite resistant operon(ter operon)are distributed in many highly pathogenic microorganisms.These tellurite resistance genes are not only related to tellurite resistance,but also to the response of cells to a variety of environmental stimuli.However,little is known about the metabolic pathway and mechanism of tellurium resistance gene.In this work,the ter operon of Pseudomonas citronellonensis SJTE-3was used as the research target,to study its effect on the process of cell division and its mechanism.Results showed that that the overexpression of this ter operon in P.citronellonensis SJTE-3 and Escherichia coli MG1655could cause the abnormal cell division of these strains,and the cells elongated into filaments phenotype.Further E.coli MG1655 strain was used as the research strain and the key gene affecting the cell division in the ter operon was proved to be terA gene.High copy number and the overexpression of terA gene to a certain level resulted in the observed abnormal cell division.Different sources of terA gene had similar effects on cell division.Bioinformatics analysis showed that TerA protein,as a homologue of TerD protein,may form a complex with other TerD homologues in this ter operon,performing specific functions.However,TerA protein still had its own unique functions like the influence on cell division.In TerA protein,domain TerAD2 was proved to be the key functional domain to affect cell division,which containing a highly conserved Ca²⁺binding site,closely related to the function of TerA protein.The study on target genes of TerA protein showed that the transcription levels of seven cell division related genes,including slmA gene and sulA gene,were significantly up-regulated when terA gene was overexpressed.Overexpression of slmA gene and sulA gene could also make the cell present similar elongation and filamentary morphology,and the intracellular localization of SlmA protein was similar to that of TerA protein.TerA protein can affect the SlmA protein,and then act on the mitotic protein FtsZ and Min system related to Z-ring localization,causing abnormal localization or contraction of Z-ring and finally leading to abnormal cell division.In addition,the overexpression of terA gene in E.coli could enhance strain's tolerance to the oxidative stress,effectively reduce the cellular ROS level and alleviate the cytotoxicity of key tellurite resistance protein(TerCD),improving the survival rate of cells under oxidative stress and further enhancing the tellurite resistance of the strain.The effect of TerA on cell division does not lead to the cell death,only the temporary stagnation of cell division process,which was one of the survival strategies of bacteria occurred under the stress environments functioning as an adaptive change.Therefore,the effect of TerA protein on cell division is an adaptive strategy for bacteria to cope with environmental stimuli,which may be one of the reasons that tellurite resistant genes are widely existed and highly conserved in pathogens.This work can promote the function mining and mechanism analysis of ter operon,lay a foundation for the mechanism exploration and physiological significance of ter operon in pathogenic bacteria and other microorganisms,and provide clues for its rational utilization.