Transcriptomic analysis of a spiramycin Ⅰ-resistant Staphylococcus aureus mutant / 中国药科大学学报

ABSTRACT

The clinical utility of macrolide antibiotics has declined due to the appearance of resistant isolates.A spiramycin Ⅰ-resistant Staphylococcus aureus ATCC29213-R was induced and isolated with increasing the concentration of spiramycin Ⅰ,which exhibits an A→C transversion at position 2089 in the 23S rRNA gene,which is first reported in the S.aureus.A RNA-seq based transcriptomic analysis was performed to understand the overall response of resistant bacteria to spiramycin Ⅰ treatment with subinhibitory dosage.Inn this study,There are a total of 322 up-regulated and 82 down-regulated genes in spiramycin Ⅰ-treated S.aureus ATCC29213-R and 426 up regulated,838 down-regulated in spiramycin Ⅰ-treated S.aureus ATCC29213,which were identified differentially expressed compared to their control with a minimum 2-fold change (Q ＜ 0.05).Interestingly,The data showed that argH and argG transcripts,in the arginine biosynthetic pathway,were decreased by 13.51-fold and 21.45-fold,respectively,compared to the control,while the expression level of three genes involved in arginine catabolism,arcA,arcC,and argF,increased by 35-fold,18.05-fold and 30.84-fold,respectively.The results revealed that spiramycin Ⅰ could trigger the up-regulation of the genes of ACME-Arc system which allows S.aureus to survive in acidic environments of human skin.This suggesed the arginine-deiminase pathway may be a potential target for treatment of the resistant S.aureus.