2021 Fiscal Year Final Research Report
Integrated understanding of the beta-lactam resistant mechanisms in mutations responsible for the beta-lactam resistance in oxacillin susceptible MRSA
| Project/Area Number |
19K08960
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54030:Infectious disease medicine-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
相羽 由詞 自治医科大学, 医学部, 助教 (60783694)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | メチシリン耐性黄色ブドウ球菌 / MRSA / 薬剤耐性菌 / βラクタム薬 / オキサシリン感性黄色ブドウ球菌 |
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| Outline of Final Research Achievements |
Recently oxacillin-susceptible mecA-positive S. aureus (OS-MRSA) have been increasingly reported worldwide. OS-MRSA may be prone to generate the highly beta-lactam-resistant mutants following antibiotic selection due to mecA carriage, ultimately leading to beta-lactam treatment failure. The research aim is to clarify mechanisms of beta-lactam susceptibility and beta-lactam resistance acquisition by beta-lactam exposure in OS-MRSA. Genome analysis of 43 OS-MRSA revealed a high diversity of genetic background. 100 oxacillin resistant mutants generated by oxacillin exposure carried a total of 141 mutations in 46 genes and 8 intergenic regions. Among them, the mutations were most frequently identified in RNA polymerase genes (rpoBC). The mutations on rpoBC disrupted in vivo RNA synthesis and caused accumulation of ribonucleotide triphosphate and peptidoglycan precursors. It might affect oxacillin resistance in the mutants.
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| Free Research Field |
感染症学
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| Academic Significance and Societal Importance of the Research Achievements |
メチシリン耐性黄色ブドウ球菌（MRSA）は、院内感染の指標耐性菌のひとつであり、医療現場において監視が必要な耐性菌である。MRSAは、耐性遺伝子mecAを保有する。しかし、mecAを保有するにも関わらずβラクタム系抗菌薬であるオキサシリンに感性を示す「オキサシリン感性mecA陽性黄色ブドウ球菌（OS-MRSA）」が度々臨床分離される。OS-MRSAはメチシリン感性黄色ブドウ球菌と誤判定されてβラクタム薬治療が開始されると、そのβラクタム薬暴露により耐性化する可能性があることが臨床上の問題である。本研究課題では、OS-MRSAのβラクタム薬暴露による耐性化メカニズムの一端を明らかにした。
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