Effect of berberine on regulation of differential gene expression in Staphylococcus aureus
OBJECTIVE To analyze the differences in genome-wide sequence expression characteristics of Staphylo-coccus aureus strains(methicillin-sensitive and methicillin-resistant)following berberine treatment,and to analyze the disparities in the genes and regulatory pathways of MSSA and MRSA strains.METHODS The standard strains ATCC 25923 and USA300 were treated with high concentration[1/2 minimum inhibitory concentration(MIC),64 μg/ml],low concentration(1/8 MIC,16 μg/ml),and no berberine for three hours,the standard strains were sequenced using the Illumina Hiseq platform,and the differentially expressed genes(DEGs)was detected by ap-plying DEseq2 and PosionDis algorithms.The expression of ATCC 25923 and USA 300 differential genes was ana-lyzed,and the differential gene screening conditions were set to P value<0.05 and multiplicity of difference>2.RESULTS Subsequent RNA-seq sequencing revealed that the whole genome sequences of the chromosomes of ATCC 25923 and USA300 strains were 28,630,235 bp and 46,174,489 bp,respectively,with 2,154 and 2,304 genomes,and the GC content of the coding genes were found to be 35.34%and 37.09%,and the average gene si-zes were found to be 147 bp and 144 bp,respectively.In the high concentration group compared with the normal control group,MRSA had a total of 859 differential gene expressions,while MSSA had only 276 differential gene expression.In the low concentration group compared with the normal control group,MRSA had a total of 19 dif-ferential gene expressions,while MSSA had 39 differential gene expressions.There were 148 GO pathways with significant differences of pathways regulated by berberine on MSSA(P<0.05),296 GO pathways with significant differences of pathways regulated by berberine on MRSA(P<0.05),of which 48 pathways were co-regulated.Berberine was associated with 71 KEGG path ways for regulating MSSA and 104 KEGG pathways for regulating MRSA,with 43 differentially regulated pathways.CONCLUSIONS The differences in genome sequence size be-tween the two strains were relatively obvious,but there were no significant disparities in genome number,GC content of coding genes,and average gene size.By studying the differential gene expression of ATCC 25923 and USA 300 transcriptomes after the action of berberine,it was hypothesized that berberine primarily impacted the membrane polysaccharide biosynthesis protein family,toxin genes,GO pathways,and KEGG pathways to exert antibacterial effects against MSSA and MRSA.