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

•In vitro screens have very low success rate in follow up preclinical trials.•In vitro systems do not reflect the complexity of the host.•The main advantage of Drosophila is its significant similarity with humans.•Drug screens in Drosophila may increase the success of preclinical trials.

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.