Antimicrobial resistance (AMR) represents an enormous global health crisis. However, novel antimicrobial drugs to tackle AMR spread are increasingly difficult to discover and develop, thus creating a widening gap between clinical needs and drug pipeline innovation[1]. In this context, our research efforts in the recent years have been two-pronged. On the one hand, we investigated the use of nanotechnology-tailored agents as alternative antibacterial treatments that could potentiate the efficacy of already-in-use antibiotics. We successfully prepared nano-formulations of the ‘last-resort’ glycopeptide antibiotics (GPA) teicoplanin and vancomycin -clinically used for fighting severe infections caused by multi-resistant Gram-positive pathogens- by conjugating them to iron oxide nanoparticles[2,3]. In addition to presenting good stability, reduced cytotoxicity, and in vitro antimicrobial activity against a panel of Gram-positive pathogens, when concentrated by the action of an external magnet, these superparamagnetic nano-antibiotics exerted a localized inhibition on Staphylococcus aureus biofilm formation even at low GPA concentration, at which the effect of the free counterpart was negligible[3]. On the other hand, to limit the use of mammals in drug discovery and development -which determines serious ethical problems, high expenses, and long times, thus slowing down preclinical tests of new drugs-, we developed an alternative infection model based on the silkworm Bombyx mori, demonstrating its usefulness for evaluating GPA candidates against staphylococcal infections[4,5]. Recently, the infection model proved its usefulness also for acquiring data on in vivo toxicity and efficacy of the previously prepared nano-antibiotics, thus extending its potential future applications.
Integrated strategies to overcome the lack of novel antibiotics against Gram-positive pathogens
F. Berini;A. Montali;F. Gamberoni;V. Orlandi;R. Gornati;G. Bernardini;G. Tettamanti;F. Marinelli
2023-01-01
Abstract
Antimicrobial resistance (AMR) represents an enormous global health crisis. However, novel antimicrobial drugs to tackle AMR spread are increasingly difficult to discover and develop, thus creating a widening gap between clinical needs and drug pipeline innovation[1]. In this context, our research efforts in the recent years have been two-pronged. On the one hand, we investigated the use of nanotechnology-tailored agents as alternative antibacterial treatments that could potentiate the efficacy of already-in-use antibiotics. We successfully prepared nano-formulations of the ‘last-resort’ glycopeptide antibiotics (GPA) teicoplanin and vancomycin -clinically used for fighting severe infections caused by multi-resistant Gram-positive pathogens- by conjugating them to iron oxide nanoparticles[2,3]. In addition to presenting good stability, reduced cytotoxicity, and in vitro antimicrobial activity against a panel of Gram-positive pathogens, when concentrated by the action of an external magnet, these superparamagnetic nano-antibiotics exerted a localized inhibition on Staphylococcus aureus biofilm formation even at low GPA concentration, at which the effect of the free counterpart was negligible[3]. On the other hand, to limit the use of mammals in drug discovery and development -which determines serious ethical problems, high expenses, and long times, thus slowing down preclinical tests of new drugs-, we developed an alternative infection model based on the silkworm Bombyx mori, demonstrating its usefulness for evaluating GPA candidates against staphylococcal infections[4,5]. Recently, the infection model proved its usefulness also for acquiring data on in vivo toxicity and efficacy of the previously prepared nano-antibiotics, thus extending its potential future applications.
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