title: Beyond Traditional Antimicrobials: ACaenorhabditis elegansModel for Discovery of Novel Anti-infectives.
abstract: The spread of antibiotic resistance amongst bacterial pathogens has led to an urgent need for new antimicrobial compounds with novel modes of action that minimize the potential for drug resistance. To date, the development of new antimicrobial drugs is still lagging far behind the rising demand, partly owing to the absence of an effective screening platform. Over the last decade, the nematodeCaenorhabditis eleganshas been incorporated as a whole animal screening platform for antimicrobials. This development is taking advantage of the vast knowledge on worm physiology and how it interacts with bacterial and fungal pathogens. In addition to allowing forin vivoselection of compounds with promising anti-microbial properties, the whole animalC. elegansscreening system has also permitted the discovery of novel compounds targeting infection processes that only manifest during the course of pathogen infection of the host. Another advantage of usingC. elegansin the search for new antimicrobials is that the worm itself is a source of potential antimicrobial effectors which constitute part of its immune defense response to thwart infections. This has led to the evaluation of effector molecules, particularly antimicrobial proteins and peptides (APPs), as candidates for further development as therapeutic agents. In this review, we provide an overview on use of theC. elegansmodel for identification of novel anti-infectives. We highlight some highly potential lead compounds obtained fromC. elegans-based screens, particularly those that target bacterial virulence or host defense to eradicate infections, a mechanism distinct from the action of conventional antibiotics. We also review the prospect of usingC. elegansAPPs as an antimicrobial strategy to treat infections.
authors.affiliation: School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia Bangi, Malaysia.
authors.forename: Cin
authors.initials: C
authors.lastname: Kong
authors.affiliation: School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia Bangi, Malaysia.
authors.forename: Su-Anne
authors.initials: SA
authors.lastname: Eng
authors.affiliation: School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia Bangi, Malaysia.
authors.forename: Mei-Perng
authors.initials: MP
authors.lastname: Lim
authors.affiliation: School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia Bangi, Malaysia.
authors.forename: Sheila
authors.initials: S
authors.lastname: Nathan
keywords: Caenorhabditis elegans; anti-virulence; antimicrobial peptides; antimicrobials; immunomodulator