An Efficient and Novel Screening Model for Assessing the Bioactivity of Extracts against Multidrug-Resistant Pseudomonas aeruginosa Using Caenorhabditis elegans

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2011, Vol.75 (9), p.1746-1751
• Main Authors: ZHOU, Yu-meng, SHAO, Lei, LI, Ji-an, HAN, Li-zhong, CAI, Wai-jiao, ZHU, Chun-bao, CHEN, Dai-jie
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antiinfectives; Biological and medical sciences; Caenorhabditis elegans; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - microbiology; Colony Count, Microbial; Drug Resistance, Multiple, Bacterial - drug effects; Fundamental and applied biological sciences. Psychology; High-Throughput Screening Assays; Larva - growth & development; Larva - microbiology; multidrug-resistant Pseudomonas aeruginosa; Nematoda; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plants, Medicinal - chemistry; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - growth & development; Pseudomonas aeruginosa - pathogenicity; Pseudomonas Infections - drug therapy; screening model; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology
• ISSN: 0916-8451; 1347-6947; 1347-6947
• DOI: 10.1271/bbb.110290

As a large number of multidrug-resistant bacteria have emerged, and there is an urgent need for the development of new antibacterial agents. In this study, we developed a liquid-based slow killing assay to be carried out in standard 96-well microtiter plates. This screening method was designed to facilitate high-throughput screening of small molecules and extracts. In antibiotic rescue assays, the Caenorhabditis elegans multidrug-resistant Pseudomonas aeruginosa infection model displayed a high degree of drug resistance in vivo and in vitro. We used the method to screen 1,300 extracts, and found 36 extracts (2.7%) which prolonged the survival of infected nematodes, and four (0.3%) of these extracts showed in vitro and in vivo anti-multidrug resistant P. aeruginosa activity. These results indicate that the whole-animal C. elegans multidrug-resistant bacterial model can be used to screen antibacterial compounds, and can also be useful for bioactive compounds which most likely cannot be identified in vitro.