Phenotypic Plasticity Of Staphylococcus Aureus In Vancomycin Cultures

Phenotypic plasticity enables individuals to develop different phenotypes in changing environments and promotes adaptive evolution.Phenotypic changes are ubiquitous in nature,and their positive effects on organisms are obvious.In multicellular organisms,phenotypic plasticity has developed into a mature research system,but the study of bacterial phenotypic plasticity is not enough.Staphylococcus aureus is pathogenic bacteria.Its drug resistance has become an urgent global problem to be solved.In this study,the growth of 41 S.aureus under vancomycin pressure was discussed in order to obtain the related gene loci that may regulate the plasticity of growth phenotype.With three different vancomycin concentrations?0 ?g/mL,2 ?g/mL and 4 ?g/mL?,41 strains of S.aureus grew for 48 hours in BHI and their OD600 values were measured at 14 time points.The growth curves and maximum growth rates of all strains were plotted.The phenotype and genotype were correlated by multivariate genome-wide association analysis?GWAS?,and significant SNPs were screened by three multivariate GWAS of O?g/mL and 2?g/mL voncomycin,0?g/mL and 4 ?g/mL vancomycin,0 ?g/mL,2 ?g/mL,and 4 ?g/mL vancomycin.Through three GWAS results,many significant loci involved in cell membrane,amino acid and nucleotide synthesis were obtained,and large numbers of loci located in non-coding regions and gene functions have not been studied.For each GWAS,the significant loci were listed in descending order by-logP value,and SNP loci with high frequency and-logP value were screened.Finally,four loci?SNP738836,264897,1394043 and 965494?with high frequency and high-logP value were obtained,including three loci located in known functional proteins and one locus located in non-coding region.SNP738836 is located between SAOUHSC 00755 and glxK,in which SAOUHSC 00755 is related to eDNA release.In the process of biofilm formation,eDNA release represents the peak of cell membrane synthesis.SNP264897 is located on SAOUHSC₀0246,which encodes a multi-drug resistant pump.SNP1394043 is located on ebh.The mutation of ebh increases the volume of staphylococcal cells and changes the cross wall of the synthesis and assembly of a peptideglycan.SNP965494 is located on atiL.The two proteins encoded by atil are related to the cell wall lysis activity of Micrococcus haemolyticus,Bacillus subtilis and Lugdenia.In this study,three high frequency and significant genes and one non-coding region were obtained by multivariate GWAS analysis of different experimental groups.Based on multivariate GWAS,the phenotypic plasticity of S.aureus under vancomycin conditions was investigated at genome-wide level.Potential growth regulator genes were revealed,which provided evidence for multivariate GWAS as a tool for finding related genes.