Drosophila melanogaster: a first step and a stepping-stone to anti-infectives

Abstract

Following an expansion in the antibiotic drug discovery in the previous century, we now face a bottleneck in the production of new anti-infective drugs. Traditionally, chemical libraries are screened either using in vitro culture systems or in silico to identify and chemically modify small molecules with antimicrobial properties. Nevertheless, almost all compounds passing through in vitro screening fail to pass preclinical trials. Drug screening in Drosophila offers to fill the gap between in vitro and mammalian model host testing by eliminating compounds that are toxic or have reduced bioavailability and by identifying others that may boost innate host defence or selectively reduce microbial virulence in a whole-organism setting. Such alternative screening methods in Drosophila, while low-throughput, may reduce the cost and increase the success rate of preclinical trials.

In vivo Antibacterial Activity of Green Algae Ulva reticulata against Staphylococcus aureus in Drosophila Model of Infection

“…10 To make things worse, there is no guarantee that the antibiotic candidates with positive results in an in vitro experiment will yield similar results in the trial stage using an in vivo animal model system. 7,10 Therefore, there is a high chance that valuable time and costs that have been spent during the discovery process may not bring a profitable outcome. At present, there is a vast number of original articles reporting the antibacterial activity of crude extracts prepared (or compounds isolated) from a diverse array of natural products, 12,13 including Indonesian medicinal plants.…”

“…One of the reasons for the declining in the rate of antibiotic drug discovery is the high cost of in vivo testing of antibacterial activity using mammalian model systems. 10,11 In addition, the impact of ethical issues raised by the use of the traditional established mammalian model of bacterial infection is a challenge when examining the effect of many antibiotic candidates in parallel, thus increasing the assessment period. 10 To make things worse, there is no guarantee that the antibiotic candidates with positive results in an in vitro experiment will yield similar results in the trial stage using an in vivo animal model system.…”

“…10,11 In addition, the impact of ethical issues raised by the use of the traditional established mammalian model of bacterial infection is a challenge when examining the effect of many antibiotic candidates in parallel, thus increasing the assessment period. 10 To make things worse, there is no guarantee that the antibiotic candidates with positive results in an in vitro experiment will yield similar results in the trial stage using an in vivo animal model system. 7,10 Therefore, there is a high chance that valuable time and costs that have been spent during the discovery process may not bring a profitable outcome.…”

“…[23][24][25] Drosophila melanogaster have been widely suggested as a suitable host for several pathogenic bacteria known to cause devastating infections in humans such as Staphylococcus aureus, 11,26 Pseudomonas aeruginosa, 27 Listeria monocytogenes, 28 Burkholderia spp., 29 and Bacillus anthracis. 30 In addition to that, with its high degree of genetic similarity with human, cheap maintaining costs, and poses almost no ethical issues, 10,16,17 D. melanogaster offers great advantages as an in vivo model system in antibacterial drug discovery research. Capitalizing on such advantages, in the current study, we tested the application of Drosophila model of bacterial infection as an in vivo platform to assess the antibacterial effect of Ulva reticulata extract, a particular sample that was shown to have a strong in vitro antibacterial activity against S. aureus in the preliminary in vitro experiment.…”

Parallels Between Mammals and Flies in Inflammatory Bowel Disease

“…The simpler immune system of the fly reduces the complexity and enables the easier study of human intestinal microbes and their relation to the host defense responses that lead to disease (Panayidou et al 2014). Furthermore, infectious disease and cancer studies in Drosophila are facilitated by established techniques for large scale in vivo RNAi and drug testing (Tzelepis et al 2013).…”