Generating proteomic data on signalling pathways in pathogenic bacteria for the discovery of new antibiotic target molecules.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06455
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Hiroshima University
• Principal Investigator: Kinoshita Emiko 広島大学, 医系科学研究科(薬), 助教 (40379912)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ヒスチジンキナーゼ / ２成分伝達系 / レスポンスレギュレータ / リン酸化 / Phos-tag / 阻害剤 / 抗生物質

Outline of Final Research Achievements

In recent years, the development of inhibitors of histidine kinase (HK), which constitutes a signalling pathway involved in drug resistance, virulence development and growth potency of pathogenic bacteria, has been pursued in Japan and abroad. The aim of this study was to accumulate data on the comprehensive analysis of the relationship between signal activation by HK and external environmental factors using the ‘Fostag’ technique for analysing HK phosphorylation, so that the target molecules of novel antibiotics such as inhibitors can emerge. We created pseudo-E. coli in which several types of HKs, such as EvgS, which is considered to be involved in the development of virulence in pathogenic E. coli and dysenteriae, and HKs involved in drug resistance, were constantly expressed, and examined the transcriptome changes associated with the expression of these HKs.

Free Research Field

薬学

Academic Significance and Societal Importance of the Research Achievements

薬剤耐性病原細菌は世界的脅威であり，それらの増殖，病原性，薬剤耐性遺伝子の発現にかかわる細菌独特のタンパク質は，既存の薬剤とは全く異なる作用店を持つ薬剤耐性菌にも有効な次世代型抗菌薬として期待され，開発が望まれている。しかし，それらのタンパク質の機能を俯瞰できるプロテオームデータはまだ揃っていない。それらの機能に迫るデータを蓄積することは，新しい抗菌薬の作用点の発見，開発に役立つ。