Identification of functional factors of Mycobacterium tuberculosis M strain using non-synonymous SNP

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08347
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Hokkaido University of Science (2018); Hokkaido Pharmaceutical University School of Pharmacy (2016-2017)
• Principal Investigator: Maeda Shinji 北海道科学大学, 薬学部, 教授 (50250212)
• Co-Investigator(Renkei-kenkyūsha): FUJIWARA nagatoshi (80326256) ; WADA takayuki (70332450)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 結核菌 / ゲノム / 一塩基多型

Outline of Final Research Achievements

M strains that form a large cluster of Mycobacterium tuberculosis isolated in Japan are one of the Beijing modern-type strains that are reported to be highly pathogenic. The whole genome analysis of the M strain revealed that 45 genes have a single nucleotide polymorphism (SNP) accompanied by amino acid substitution (non-synonymous).
Focusing on these genes, plasmids were constructed having the wild type nucleotide (H37Rv sequence) and the mutation type (M strain sequence). The transformation efficiency and the growth rate were compared between them. The fatty acid metabolic enzymes, fadD25 and fadB3 may be involved in infectivity and virulence because the transformation efficiency was higher when the M strain mutant type was expressed.

Free Research Field

微生物学

Academic Significance and Societal Importance of the Research Achievements

M株のゲノム解析により得られた非同義一塩基多型を持つ遺伝子解析によって、結核菌を含む抗酸菌では、脂肪酸代謝酵素のアミノ酸置換により、形質転換効率が高くなった。このように、脂肪酸代謝酵素の構造変化により表現型に変化が生じることは、脂肪酸合成酵素が病原性や感染性などに関与している可能性を示唆する。重要な病原性因子（遺伝子）が特定できれば、より危険度の高い結核菌を迅速に鑑別することが可能になる。また、新規抗微生物薬の標的となる反応を特定することができる。