Drug repurposing for antivirulence therapy against opportunistic bacterial pathogens.

摘要: 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 being developed by pharmaceutical industry. Over last decades, progress in understanding pathogenic process infections has led researchers to focus on virulence factors as potential targets for ‘antivirulence' drugs, i.e. compounds which inhibit ability bacteria cause damage host, opposed inhibition growth typical antibiotics. Hundreds inhibitors been examined date vitro and/or animal models, only were entered into clinical trials none approved, thus hindering validation antivirulence therapy. To breathe life research speed-up its transfer clinic, activities also sought drugs already approved different therapeutic purposes humans. If effective, these could be repositioned therapy an easier faster clinic. In this work we summarize approaches identification repurposing candidates with activities, discuss challenges opportunities related drug repurposing. While approach undoubtedly holds promise boosting research, some important issues remain addressed order make viable alternatives traditional antibacterials. * ADMET, : absorption, distribution, metabolism, excretion toxicity; c-di-GMP, cyclic diguanylate; FDA, US Food Drug Administration; MIC, minimum inhibitory concentration; QS, quorum sensing