Effects of sub-inhibitory concentration of imipenem on proliferation in vitro and mRNA expression levels of MRSA virulence related genes / 吉林大学学报(医学版)

ABSTRACT

Objective:To explore the effect of sub-inhibitory concentration of imipenem on the bio-activities of methicillin resistant Staphylococcus aureus(MRSA) and illuminate the inhibitory effects of carbapenem antibioty on the activity of MRSA and their mechanisms,and to provide the basis for using the carbapenem antibiotics in the treatment of MRSA infection.Methods:Five ST239 type of MRSA clinical isolates were selected and were co-cultured with 1/10 and 1/2 minimal inhibitory concentration (MIC) of imipenem for 1.5,6.0 and 12.0 h,which were divided into control group(no imipenem),1/10MIC group(1/10MIC of imipenem),and 1/2MIC group(1/2MIC of imipenem).Fluorescent quantitative real-time PCR method was used to determine the relative mRNA expression levels of virulence-related genes fibronectin A(fnbA),staphylococcal protein A(spa),α-hemolysin(Hla),leukocidin D(lek-D),leukocidin E(lek-E),and enterotoxin A in various groups;Spectrophotometry was used to detect the proliferation activity of MRSA strains in various groups in vitro.Results:After co-culture for 6.0 and 12.0 h,the proliferation activities of 5 trains of MRSA in 1/2MIC group in vitro were significantly decreased compared with control group (P<0.01).The relative mRNA expression levels of 6 virulence-related genes of 5 strains of MRSA in 1/10MIC and 1/2MIC groups were significantly decreased compared with control group(P<0.01).After co-culture for 12.0 h,the mRNA expressions of all the tested virulence-related genes were not found.Conclusion:The sub-inhibitory concentration of imipenem shows obviously inhibitory effect on the mRNA expressions of multiple virulence-related genes of ST 239 type of MRSA strains,and higher concentration of imipenem can suppress the proliferation of MRSA strains in vitro.Imipenem shows the potential value in the treatment of the severe MRSA infected patients.