Rapid evaluation of antibacterial effects and drug selection using bacterial RNA

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20950
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy; Bacteriology (including mycology)
• Research Institution: Gunma University
• Principal Investigator: Hideaki Yashima 群馬大学, 医学部附属病院, 助教 (60773512)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 感染症 / 抗菌薬 / RNA / 効果判定

Outline of Final Research Achievements

In order to construct the optimal drug selection method for treatment of infectious diseases, the nucleic acid that fluctuates relating the growth rate of bacteria called pre-rRNA was used as a marker, and a rapid method for determining the effect of antibacterial drug was examined.
As a result of examining the relationship between bacterial growth and pre-rRNA of Pseudomonas aeruginosa PAO-1 strain, it is possible to determine sensitivity to bacteria using pre-rRNA value per bacteria 3 hours after meropenem exposure. On the other hand, exposure to ciprofloxacin resulted in the greater reduction in per-bacterial pre-rRNA levels compared to meropenem, and no significant change was seen in tobramycin. We found that the profile of pre-rRNA has features of each drug of mechanism of action. Although we have been examining the determination method common to each drug, we have not yet built a model, and are conducting a comprehensive search of bacteria-derived proteins.

Free Research Field

臨床薬理学

Academic Significance and Societal Importance of the Research Achievements

既存の培養法に基づいた薬剤感受性試験や患者の炎症マーカーを用いた臨床的な抗菌薬の効果判定は数日間の時間を要するが、原因微生物由来のpre-rRNAを用いた本法では、細菌からの核酸抽出、逆転写反応、定量PCRのステップを約6時間程度で測定可能であり、迅速さの点で優れていると言える。抗菌薬ごとに精度よく解析できるモデルを構築できれば細菌の濃度が比較的多い検体（尿や喀痰）を用いて早期に効果判定ができると考えられる。実臨床でこの検査が実装されれば、耐性菌が増えている昨今での感染症治療において適切な治療選択をより早期に行うことが可能となる。