
임상 분리주의 저산소 적응 메커니즘은 포도당 신생합성, 제7형 분비 시스템, 시스테인 탈황효소 등의 유전자 필수성 증가와 관련이 있으며, 이는 마우스 폐 감염 실험에서도 확인되었다.


coremsg

Mycobacterium intracellulare is a major etiological agent of the recently expanding Mycobacterium avium–intracellulare complex pulmonary disease (MAC-PD). Therapeutic regimens that include a combination of macrolides and antituberculous drugs have been implemented with limited success. To identify novel targets for drug development that accommodate the genomic diversity of M. avium–intracellulare , we subjected eight clinical MAC-PD isolates and the type strain ATCC13950 to genome-wide profiling to comprehensively identify universally essential functions. Among these strains, we identified 131 shared essential or growth-defect-associated genes. Unlike the type strain, the clinical strains showed an increased requirement for genes involved in gluconeogenesis and the type VII secretion system under standard growth conditions, the same genes required for hypoxic pellicle-type biofilm formation in ATCC13950. Consistent with the central role of hypoxia in the evolution of M. intracellulare , the clinical MAC-PD strains showed more rapid adaptation to hypoxic growth than the type strain. Importantly, the increased essentiality of hypoxic fitness genes was confirmed in a mouse lung infection model. These findings confirm the concordant gene essentiality under hypoxic conditions in vitro and hypoxia-related conditions in vivo , and highlight the importance of using clinical strains and host-relevant growth conditions to identify high-value targets for drug development.

### Competing Interest Statement

The authors have declared no competing interest.

Functional genomics reveals the mechanism of hypoxic adaptation in nontuberculous mycobacteria

다양한-임상-분리주를-이용한-비결핵-마이코박테리아의-저산소-적응-메커니즘-규명


다양한 임상 분리주를 이용한 비결핵 마이코박테리아의 저산소 적응 메커니즘 규명
