Antibiotic resistance is a serious public health concern at the global level. Available antibiotics have saved millions of lives, but are progressively losing their efficacy against many bacterial pathogens, and very few new antibiotics are being developed by the pharmaceutical industry. Over the last few decades, progress in understanding the pathogenic process of bacterial infections has led researchers to focus on bacterial virulence factors as potential targets for ‘antivirulence' drugs, i.e. compounds which inhibit the ability of bacteria to cause damage to the host, as opposed to inhibition of bacterial growth which is typical of antibiotics. Hundreds of virulence inhibitors have been examined to date in vitro and/or in animal models, but only a few were entered into clinical trials and none were approved, thus hindering the clinical validation of antivirulence therapy. To breathe new life into antivirulence research and speed-up its transfer to the clinic, antivirulence activities have also been sought in drugs already approved for different therapeutic purposes in humans. If effective, these drugs could be repositioned for antivirulence therapy and have an easier and faster transfer to the clinic. In this work we summarize the approaches which have led to the identification of repurposing candidates with antivirulence activities, and discuss the challenges and opportunities related to antivirulence therapy and drug repurposing. While this approach undoubtedly holds promise for boosting antivirulence drug research, some important issues remain to be addressed in order to make antivirulence drugs viable alternatives to traditional antibacterials.
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Cover Image
Cover Image
Three derivatives of one Streptomyces species showing variations in morphological development and pigment production. In this issue, Rebecca Devine, Matthew Hutchings and Neil Holmes explore how the use of new technologies, including improved culture-dependent and -independent techniques, combined with searching underexplored environments, promises to identify a new generation of antibiotics from actinomycete bacteria such as Streptomyces. See pages 1–12 for further details. Image kindly provided by Paul A. Hoskisson (University of Strathclyde, UK).
Drug repurposing for antivirulence therapy against opportunistic bacterial pathogens
Daniel Walker, Giordano Rampioni, Paolo Visca, Livia Leoni, Francesco Imperi; Drug repurposing for antivirulence therapy against opportunistic bacterial pathogens. Emerg Top Life Sci 21 April 2017; 1 (1): 13–22. doi: https://doi.org/10.1042/ETLS20160018
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