Identification and development of anti-persister compounds as a new class of antibiotics to treat chronic infection

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15128
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: Chiba University
• Principal Investigator: Yamamoto Tomoko 千葉大学, 真菌医学研究センター, 特任教授 (60110342)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 難治性感染症薬 / anti-persister / ClpP

Outline of Final Research Achievements

Chronic infection is often difficult to treat, even when caused by a pathogen that is not resistant to antibiotics. In most cases, chronic infections are accompanied by dormant persisters. In this study, we aim to identify anti-persister compounds toward a goal of development of antibiotics for chronic infection. Our previous studies on ClpXP protease allowed us to hypothesize that the dysregulation of proteolysis by activation of ClpP core in the absence of the regulatory ClpX may corrupt physiology of dormant persisters. We conducted high-through-put screening of compounds with activity provoking ClpP by exploiting the chemical libraries. We have found that one of the hit-compounds, ACP1b with originally no anti-bacterial activity can kill a variety of bacteria including an opportunistic pathogen P. aeruginosa, in combination with an inhibitor of bacterial efflux-pump. This study will provide innovative perspectives on developing a new class of antibiotics to treat chronic infection.

Free Research Field

細菌学