Abstract
The past few decades have seen alarming rates of antimicrobial drug resistance. This trend paralleled a lack of conventional methods of discovery of antibiotics with novel mechanisms of action. Although use of mammalian models remains indispensable for preclinical testing of new antimicrobial compounds, combating emerging multidrug-resistant microbial pathogens may require the use of robust, high-throughput experimental systems that can accelerate drug development. The recent discovery of striking similarities in innate immune signaling pathways between Drosophila melanogaster and mammals has led to a surge in the use of this minihost as an alternative model in studying a variety of infectious diseases. Several genetic screens for microbial pathogenicity in Drosophila identified virulence traits shown to be important for infection in mammals that may serve as targets for future drug development. In addition, conventional antimicrobial agents retain full activity in D. melanogaster infection models, which may pave the way for use of this minihost for high-throughput antimicrobial drug screening. Finally, the availability of genetic tools that allow for conditional inactivation of almost every gene in D. melanogaster is anticipated to result in the discovery of novel immunomodulatory mechanisms of action of newly identified antimicrobial compounds. Overall, the powerful genetics of and capacity for large-scale screening in D. melanogaster make this minihost a promising complementary model that may result in a new paradigm in antimicrobial drug discovery. However, antimicrobial drug discovery in such heterologous, phylogenetically disparate minihosts as the fruit flies, would still require further validation in mammalian models.
Keywords: Drosophila melanogaster, antimicrobials, mini-host models, drug discovery, high-throughput screening, melanogaster, indispensable, immunocompromised, pathogenicity, phylogenetically, transcriptomes, peptidoglycan, metchnikowin, drosomycin, diptericin, attacin, cecropin, inoculum, Aspergillus, siderophore
Current Pharmaceutical Design
Title: Drosophila melanogaster As a Model Host for the Study of Microbial Pathogenicity And the Discovery of Novel Antimicrobial Compounds
Volume: 17 Issue: 13
Author(s): Georgios Chamilos, George Samonis and Dimitrios P. Kontoyiannis
Affiliation:
Keywords: Drosophila melanogaster, antimicrobials, mini-host models, drug discovery, high-throughput screening, melanogaster, indispensable, immunocompromised, pathogenicity, phylogenetically, transcriptomes, peptidoglycan, metchnikowin, drosomycin, diptericin, attacin, cecropin, inoculum, Aspergillus, siderophore
Abstract: The past few decades have seen alarming rates of antimicrobial drug resistance. This trend paralleled a lack of conventional methods of discovery of antibiotics with novel mechanisms of action. Although use of mammalian models remains indispensable for preclinical testing of new antimicrobial compounds, combating emerging multidrug-resistant microbial pathogens may require the use of robust, high-throughput experimental systems that can accelerate drug development. The recent discovery of striking similarities in innate immune signaling pathways between Drosophila melanogaster and mammals has led to a surge in the use of this minihost as an alternative model in studying a variety of infectious diseases. Several genetic screens for microbial pathogenicity in Drosophila identified virulence traits shown to be important for infection in mammals that may serve as targets for future drug development. In addition, conventional antimicrobial agents retain full activity in D. melanogaster infection models, which may pave the way for use of this minihost for high-throughput antimicrobial drug screening. Finally, the availability of genetic tools that allow for conditional inactivation of almost every gene in D. melanogaster is anticipated to result in the discovery of novel immunomodulatory mechanisms of action of newly identified antimicrobial compounds. Overall, the powerful genetics of and capacity for large-scale screening in D. melanogaster make this minihost a promising complementary model that may result in a new paradigm in antimicrobial drug discovery. However, antimicrobial drug discovery in such heterologous, phylogenetically disparate minihosts as the fruit flies, would still require further validation in mammalian models.
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Chamilos Georgios, Samonis George and P. Kontoyiannis Dimitrios, Drosophila melanogaster As a Model Host for the Study of Microbial Pathogenicity And the Discovery of Novel Antimicrobial Compounds, Current Pharmaceutical Design 2011; 17 (13) . https://dx.doi.org/10.2174/138161211795703744
DOI https://dx.doi.org/10.2174/138161211795703744 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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