2015 Fiscal Year Final Research Report
Exploitation of pathogenic gastrointestinal bacteria specific molecular tageting therapy
| Project/Area Number |
26670065
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Environmental and hygienic pharmacy
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SAKAKIBARA YASUBUMI 慶應義塾大学, 理工学部, 教授 (10287427)
TSUGAWA HITOSHI 慶應義塾大学, 医学部, 助教 (30468483)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Keywords | Helicobacter pylori / 鉄 / FecA1 / 除菌療法 / 酸化ストレス / in silico / メトロニダゾール |
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| Outline of Final Research Achievements |
Superoxide dismutase (SodB) of H. pylori plays an indispensable role in the development of drug resistance against metronidazole. The activation of SodB requires Fe2+ supply through FecA1, suggesting that FecA1 is a possible target for a novel eradication therapy. By in silico screening, we explored FecA1-binding compounds and identified nordihydroguaiaretic acid (NDGA), that reduced intrabacterial Fe2+ levels and SodB activity and then increased the H2O2 sensitivity to the same levels observed in fecA1-deletion mutants. NDGA decreased the colonization density of H. pylori in the mouse stomach, indicating the repression of gastric mucosal-colonization of H. pylori via inhibition of intracellular Fe2+ uptake by FecA1. In addition, NDGA also increased the in vitro H2O2 sensitivity of Salmonella typhimurium and enteropathogenic E. coli. These results suggest that NDGA might be effective for the development of a novel therapy selectively against inflammogenic enteropathogenic bacteria.
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| Free Research Field |
消化器内科学
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