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

被引:24
作者
Zhou, Yu-meng [1 ]
Shao, Lei [1 ]
Li, Ji-an [1 ]
Han, Li-zhong [2 ]
Cai, Wai-jiao [3 ]
Zhu, Chun-bao [1 ]
Chen, Dai-jie [1 ]
机构
[1] Shanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, Shanghai 200040, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Ruijin Hosp, Sch Med, Shanghai 200025, Peoples R China
[3] Fuden Univ, Huashan Hosp, Inst Integrat Chinese & Western Med, Shanghai 200040, Peoples R China
关键词
antiinfectives; Caenorhabditis elegans; multidrug-resistant Pseudomonas aeruginosa; screening model; MEDICINAL-PLANTS; INNATE IMMUNITY; IDENTIFICATION; INFECTIONS; VIRULENCE; HOST; MECHANISMS;
D O I
10.1271/bbb.110290
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1746 / 1751
页数:6
相关论文
共 28 条
  • [1] Attenuation of Pseudomonas aeruginosa virulence by medicinal plants in a Caenorhabditis elegans model system
    Adonizio, Allison
    Leal, Sixto M., Jr.
    Ausubel, Frederick M.
    Mathee, Kalai
    [J]. JOURNAL OF MEDICAL MICROBIOLOGY, 2008, 57 (07) : 809 - 813
  • [2] Antifungal chemical compounds identified using a C-elegans pathogenicity assay
    Breger, Julia
    Fuchs, Beth Burgwyn
    Aperis, George
    Moy, Terence I.
    Ausubel, Frederick M.
    Mylonakis, Eleftherios
    [J]. PLOS PATHOGENS, 2007, 3 (02) : 168 - 178
  • [3] High-throughput screening of small molecules for bioactivity and target identification in Caenorhabditis elegans
    Burns, Andrew R.
    Kwok, Trevor C. Y.
    Howard, Al
    Houston, Ed
    Johanson, Karl
    Chan, Anthony
    Cutler, Sean R.
    McCourt, Peter
    Roy, Peter J.
    [J]. NATURE PROTOCOLS, 2006, 1 (04) : 1906 - 1914
  • [4] Clinical and Laboratory Standards Institute, 2006, M100S16 CLSI
  • [5] Clinical and Laboratory Standards Institute, 2006, M2A9 CLSI
  • [6] TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM
    Couillault, C
    Pujol, N
    Reboul, J
    Sabatier, L
    Guichou, JF
    Kohara, Y
    Ewbank, JJ
    [J]. NATURE IMMUNOLOGY, 2004, 5 (05) : 488 - 494
  • [7] Lethal paralysis of Caenorhabditis elegans by Pseudomonas aeruginosa
    Darby, C
    Cosma, CL
    Thomas, JH
    Manoil, C
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) : 15202 - 15207
  • [8] Pseudomonas aeruginosa Suppresses Host Immunity by Activating the DAF-2 Insulin-Like Signaling Pathway in Caenorhabditis elegans
    Evans, Eric A.
    Kawli, Trupti
    Tan, Man-Wah
    [J]. PLOS PATHOGENS, 2008, 4 (10)
  • [9] Tackling both sides of the host-pathogen equation with Caenorhabditis elegans
    Ewbank, JJ
    [J]. MICROBES AND INFECTION, 2002, 4 (02) : 247 - 256
  • [10] Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and impact on treatment
    Hancock, REW
    Speert, DP
    [J]. DRUG RESISTANCE UPDATES, 2000, 3 (04) : 247 - 255