[ODP5E] e. その他

[ODP-110/WS9-6] GWASアプローチによる肺 MAC症の病態に関連する細菌側因子の探索

○矢野 大和¹，西内 由紀子²，有川 健太郎³，大田 篤⁴，三木 真理⁵，丸山 史人⁴，木田 博⁵，北田 清悟⁵，岩本 朋忠³ (¹東北大学・大学院生命科学研究科，²大阪市立大学・大学院医学研究科，³神戸市環境保健研究所，⁴広島大学・未来共生建造環境センター，⁵国立病院機構大阪利根山医療センター)

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.