Characterization of bacterial small-colony variants causing antimicrobial resistance using omics analysis and establishment of their microbiological assays

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16517
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Ota Yusuke 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (90868530)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 小型コロニー形成細菌 / 薬剤耐性 / 全ゲノム解析 / RNAシーケンス解析 / 臨床微生物検査 / カイコ細菌感染モデル

Outline of Final Research Achievements

This study aimed to characterize the genetics and phenotypic features of bacterial small colony variants (SCVs) involved in persistent infections and to develop an appropriate detection and control approach for SCVs. Whole-genome sequencing analysis was performed to identify genetic variants involved in SCV formation. RNA sequencing analysis was used to comprehensively demonstrate changes in gene expression levels related to metabolism and virulence. Phenotypic changes in virulence factors such as biofilms were experimentally revealed. Furthermore, infection experiments using epithelial cells and silkworms were conducted to clarify the relationship with SCV changes. On the other hand, SCV testing was optimized by adding supplements suitable for SCV growth to conventional microbiological tests.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

薬剤耐性対策は喫緊の課題で、様々なアクションプランが推進されているが、対策の一つとしてSCVsに着目した感染制御の研究はない。またSCVsのゲノム解析や表現型解析により多角的・網羅的に解析した研究はほとんどなく、本研究によりSCVsの解析データが蓄積され、適切な検出法や抗菌薬投与条件の設定も含めたSCVsの制御法を確立できれば、AMR対策の新たな戦略に繋がる。更にはSCVsの遺伝学的・臨床細菌学的な特徴を明らかにすることで、様々な菌種におけるSCVsの関与や、持続性・再発性感染症のようなSCVsの関与が疑われる感染症の病態理解が進み、新たな診断・治療法の開発につながる臨床的発展性が期待できる。