| Popis: |
Background Daptomycin (DAP) is a cyclic lipopeptide antibiotic with potent bactericidal activity against gram-positive bacteria, and use to treat infections due to methicillin-resistant Staphylococcus aureus (MRSA). It was reported that MprF that is bacterial membrane protein and affect to DAP non-susceptible (DAP-NS), and it was generally considered that electrically repulsion by MprF mutation was thought to be contributed to DAP-NS. However, a lot of mechanisms were proposed previously and still controversial. Therefore, in this study, we found new MprF mutations from clinical MRSAs then introduced those MprF mutations into sequenced strain ( Staphylococcus aureus N315) in order to evaluate those effects to DAP-NS. Results We analysed the drug susceptibility profile of three MRSA clinical isolates and performed MprF sequence. Two of the three MRSA isolates showed DAP-NS and had different mutations of MprF (N450_I451 insI) and MprF (T345P), which have not been reported before. Then the mutations we identified were introduced into Staphylococcus aureus N315 (S. aureus N315), and we evaluated its susceptibility profile and positive charge of cell envelop to elucidate effect of DAP susceptbility. The MIC of DAP was increased by introduction of these mutations into S. aureus N315. In addition, the positive charge of the cell membrane was significantly increased in MprF(T345P), but not in MprF(N450_I451 insI). Conclusions These findings suggest that the two novel mutations contribute to DAP-NS. Furthermore, we suggested that the mechanism of DAP-NS was different depending on the mutation type and/or position of the amino acid. |
