Identification of an unidentified clarithromycin resistance mechanism in pulmonary MAC disease and evaluation of the efficacy of novel agents.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15966
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Fukano Hanako 国立感染症研究所, ハンセン病研究センター 感染制御部, 主任研究官 (40807541)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 非結核性抗酸菌症 / 薬剤耐性 / 新規抗菌薬開発

Outline of Final Research Achievements

In contrast to the decrease in the number of TB patients in Japan, the number of patients with non-tuberculous Mycobacterium tuberculosis (NTM) disease has been increasing markedly and is an emerging infectious disease with more than 140,000 patients. 19,000 new cases of pulmonary NTM disease were reported in 2014, almost the same number as TB patients, and the number of patients is expected to continue increasing. Pulmonary MAC, which accounts for about 90% of pulmonary NTMs, is treated with multidrug combination therapy using clarithromycin as the key drug, but the emergence of resistant strains during the course of treatment makes radical cure extremely difficult. Although point mutations in the 23S rRNA gene are understood to be the cause of macrolide resistance, in this study, we found the existence of CAM-resistant strains that do not have mutations in the 23S rRNA gene.

Free Research Field

微生物学

Academic Significance and Societal Importance of the Research Achievements

肺NTM症の約9割を占める肺MAC症の治療にはクラリスロマイシン(CAM)をキードラッグとした多剤併用療法が実施されるが、治療途中のCAM耐性菌出現により根治は極めて困難となり、CAM耐性肺MAC症患者の予後が多剤耐性結核患者と同等に悪い。他属菌におけるマクロライド耐性化因子の研究では、23S rRNA遺伝子上のドメインⅤにおける点突然変異のほかに膜透過性の変化や多剤排出トランスポーターの活性化等が理解されているが、NTMにおいては同遺伝子上の点突然変異のみしか理解されていない。また、CAM耐性化肺MAC症の予後が非常に悪いことからCAMに代わる新規抗菌化合物の開発が待たれている。