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
  • [11] Severe Pseudomonas aeruginosa infections -: Tackling the conundrum of drug resistance
    Hauser, AR
    Sriram, P
    [J]. POSTGRADUATE MEDICINE, 2005, 117 (01) : 41 - 48
  • [12] Studying host-pathogen interactions and innate immunity in Caenorhabditis elegans
    Kim, Dennis
    [J]. DISEASE MODELS & MECHANISMS, 2008, 1 (4-5) : 205 - 208
  • [13] A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity
    Kim, DH
    Feinbaum, R
    Alloing, G
    Emerson, FE
    Garsin, DA
    Inoue, H
    Tanaka-Hino, M
    Hisamoto, N
    Matsumoto, K
    Tan, MW
    Ausubel, FM
    [J]. SCIENCE, 2002, 297 (5581) : 623 - 626
  • [14] daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans
    Kimura, KD
    Tissenbaum, HA
    Liu, YX
    Ruvkun, G
    [J]. SCIENCE, 1997, 277 (5328) : 942 - 946
  • [15] A small-molecule screen in C-elegans yields a new calcium channel antagonist
    Kwok, TCY
    Ricker, N
    Fraser, R
    Chan, AW
    Burns, A
    Stanley, EF
    McCourt, P
    Cutler, SR
    Roy, PJ
    [J]. NATURE, 2006, 441 (7089) : 91 - 95
  • [16] Caenorhabditis elegans:: An emerging model in biomedical and environmental toxicology
    Leung, Maxwell C. K.
    Williams, Phillip L.
    Benedetto, Alexandre
    Au, Catherine
    Helmcke, Kirsten J.
    Aschner, Michael
    Meyer, Joel N.
    [J]. TOXICOLOGICAL SCIENCES, 2008, 106 (01) : 5 - 28
  • [17] Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa Caenorhabditis elegans pathogenesis model
    Mahajan-Miklos, S
    Tan, MW
    Rahme, LG
    Ausubel, FM
    [J]. CELL, 1999, 96 (01) : 47 - 56
  • [18] High-Throughput Screen for Novel Antimicrobials using a Whole Animal Infection Model
    Moy, Terence I.
    Conery, Annie L.
    Larkins-Ford, Jonah
    Wu, Gang
    Mazitschek, Ralph
    Casadei, Gabriele
    Lewis, Kim
    Carpenter, Anne E.
    Ausubel, Frederick M.
    [J]. ACS CHEMICAL BIOLOGY, 2009, 4 (07) : 527 - 533
  • [19] Identification of novel antimicrobials using a live-animal infection model
    Moy, Terence I.
    Ball, Anthony R.
    Anklesaria, Zafia
    Casadei, Gabriele
    Lewis, Kim
    Ausubel, Frederick M.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (27) : 10414 - 10419
  • [20] Update on Pseudomonas aeruginosa and Acinetobacter baumannii infections in the healthcare setting
    Navon-Venezia, S
    Ben-Ami, R
    Carmeli, Y
    [J]. CURRENT OPINION IN INFECTIOUS DISEASES, 2005, 18 (04) : 306 - 313