Tsugawa Hitoshi
Department of Biochemistry & Integrative Medical Biology, School of Medicine, Keio University.
Nihon Saikingaku Zasshi. 2014;69(4):565-75. doi: 10.3412/jsb.69.565.
Chronic infection with Helicobacter pylori is involved in a variety of clinical outcomes including gastric cancer. In the present study, we focused on the infection strategies of H. pylori associated with establishment of chronic infection. As a result, the following four findings revealed. 1) alpha-ketoglutarate oxidoreductase (KOR) is an essential survival enzyme for energy metabolism in the coccoid form of H. pylori, and inactivation of the KOR activity exerted a potent bactericidal action against H. pylori by preventing induction of the coccoid form. 2) SodB expression is derepressed by amino acids mutation of ferric uptake regulator (Fur), which is associated with the development of Metronidazole resistance. 3) FecA1 is an important determinant of the host-colonization ability through Fe(2+) supply to SodB, suggesting that FecA1 may be a possible target for the development of a novel bactericidal drug. 4) Intracellular CagA oncoprotein is degraded by autophagy and therefore short lived. However, in the CD44v9-expressing gastric cells, CagA specifically accumulated through the repression of autophagy induction.
幽门螺杆菌的慢性感染与包括胃癌在内的多种临床结局有关。在本研究中，我们聚焦于与慢性感染建立相关的幽门螺杆菌感染策略。结果，揭示了以下四项发现。1）α-酮戊二酸氧化还原酶（KOR）是幽门螺杆菌球形体形式能量代谢所必需的生存酶，KOR活性的失活通过阻止球形体形式的诱导对幽门螺杆菌发挥强大的杀菌作用。2）铁摄取调节蛋白（Fur）的氨基酸突变可解除SodB表达的抑制，这与甲硝唑耐药性的产生有关。3）FecA1通过向SodB供应Fe(2+)是宿主定植能力的重要决定因素，这表明FecA1可能是开发新型杀菌药物的一个潜在靶点。4）细胞内CagA癌蛋白通过自噬降解，因此寿命较短。然而，在表达CD44v9的胃细胞中，CagA通过抑制自噬诱导而特异性积累。
