[ODP5E] e. Others

[ODP-110/WS9-6] bGWAS reveals putative bacterial factors that affect pathological outcomes of MAC lung disease

○Hirokazu Yano¹, Yukiko Nishiuchi², Kentaro Arikawa³, Atsushi Ota⁴, Mari Miki⁵, Fumito Maruyama⁴, Hiroshi Kida⁵, Seigo Kitada⁵, Tomotada Iwamoto³ (¹Grad. Sch. Life Sciences, Tohoku Univ., ²Grad Sch. Medicine, Osaka City Univ., ³Kobe Institute of Health, ⁴Center for Holobiome and Built Environment (CHOBE), Hiroshima Univ., ⁵National Hospital Organization Osaka Toneyama Medical Center)

Mycobacterium avium, the causative agent of MAC lung disease, is a recombinogenic opportunistic pathogen that has a considerable genetic diversity even in a local population. There are roughly two case types in MAC lung disease. One is the stable type that accompanies nodular bronchiectasis alone as pathological outcome. The other is the progressive type that eventually complicates fibrocavitary. What determines the case type remains an open question. In this study, we address the hypothesis that genetic factors of M. avium affect the pathological outcomes using the bacterial genome-wide association study (bGWAS) approach. We collected M. avium isolates from 107 patients falling into either of the two case types (46 stable, 61 progressive), determined their draft genome sequences, and then searched for DNA motifs associated with the case type using k-mers based GWAS. Besides known antimicrobial resistance mutations, we found the case type-associated allelic variant in the genes encoding Type I polyketide synthase, FAD-dependent monooxygenase, cytochrome P-450, and a dehydrogenase involved in arginine metabolism. This result suggests that bacterial factors in part contribute to pathological outcomes. As long-term antimicrobial treatment is a burden for patients, DNA motifs in the pathogen genome may help us design the treatment plan.