An analysis of carbapenem-inactivating effects of L-cysteine derived from human cultured cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09947
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Takemura Hiromu 聖マリアンナ医科大学, 医学部, 教授 (80301597)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 培養細胞 / カルバペネム系抗菌薬 / 不活化 / L-cysteine / A549

Outline of Final Research Achievements

At the study supported by JSPS KAKENHI Grant Number 25461525 from 2013 to 2016, we reported that antimicrobial activities of several carbapenems (Cps) decreased in the supernatants of human alveolar epithelial cell line A549. A549 supernatants and the concentration of L-cys. The A549 culture supernatants exhibited IPM-inactivating effects according to their L-cys concentrations.
In this study, we exhibited the IPM-inactivating effects of A549 supernatants were dependent on their L-Cys concentrations produced by the reduction of L-cystine (LC) in the medium, and L-Cys was prepared by the reduction of LC and other amino acids were not required for the preparation of L-Cys. As the mechanism is still unknown, FCS or serum proteins inhibited this sequential reaction, the preparation of L-Cys and IPM-inactivation dose-dependently. Moreover, the incidence of Cps-resistant Enterobacteriaceae (CRE) in Kawasaki City was relatively higher than the nationwide incidences in 2018.

Free Research Field

臨床微生物学、感染症学、感染制御学、特に宿主・微生物・抗菌薬の関係性の実験的な評価を専門とする。

Academic Significance and Societal Importance of the Research Achievements

カルバペネム耐性腸内細菌科細菌（CRE）などの薬剤耐性菌による感染症は、様々な疾患の予後に直接的に影響を及ぼす大きな問題であるが、耐性菌に対する新薬の開発は遅れ、実際に臨床の現場で使用可能になるまでには長い年月と膨大な費用が必要である。本研究ではカルバペネム系抗菌薬をヒトの細胞由来のL-システインが加水分解する機序について解析しており、抗菌薬の評価法、適正な抗菌薬療法の確立に寄与するもので、既存の抗菌薬を有効に利用することに貢献するという点で有意義である。