NANOTESTS

Fabrication and development of nanotoxicology-test bacterial arrays for the investigation of antibiotics against multi drug-resistant bacteria

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 Obiettivo del progetto (Objective)

'Bacterial resistance to antibiotics is one of medicine's most vexing challenges. Most antibiotics initially work really well, killing more than 99.9% of microbes they target. But through mutation and the selection pressure exerted by the antibiotic, a few inevitably manage to survive, and flourish as antibiotic-resistant strains. Hence, new strategies to design antibiotic to combat drug-resistant bacteria are required. Many drug delivery systems based on nanomaterials have been developed during the last decade, being the toxicology of these materials into single bacteria still not thoroughly evaluated due to the lack of reliable techniques to confine individual microbes. Prof. Whitesides' group in Harvard University (USA) is undoubtedly a world leader in this area, as it has a high international profile earned through many key contributions about novel nanofabrication methods for microbiological applications during the last 20 years. Prof. Miranda and Prof. Carrascosa (both from IMDEA Nanoscience-Spain) are the leaders of research groups working in collaboration for (i) the development of novel antibiotic strategies based on drug delivery nano-systems and (ii) biophysical aspects of cell mechanics, self-assembly properties of organic heterostructures and supramolecular nanomachines. The time is ripe to integrate the various strategies developed by Prof. Whitesides’ group to confine single living bacteria with the novel strategies for drug delivery that are being developed at IMDEA Nanoscience-Spain. The aim of the present OIF includes consolidating IMDEA expertise in the toxicological effect of nanoparticle based drug carriers into individual bacteria in order to develop a novel set of antibiotics for treatment of multi drug-resistant bacteria and to contribute to fundamental questions about bacterial biology, such as cell wall biophysics, chemical bonding and DNA conformational dynamics.'

Introduzione (Teaser)

Antibiotic resistance is proving to be a major challenge for modern medicine. To overcome this, innovative solutions for screening new drugs and interventions are required.

Descrizione progetto (Article)

Initially, antibiotics work well, but they impose strong selective pressure on pathogens, inducing them to mutate in order to survive. As a result, novel strategies are required for combating bacterial infections. Over the past few years, new drug-delivery systems based on nanomaterial carriers have been designed and tested for their efficacy in killing bacteria. However, the employed strategies are inefficient at providing sufficient information on the toxicological outcome of drug interventions.

Existing methods only evaluate the overall survival of bacteria following drug administration, and not the events that take place at the single-cell level, potentially leading to erroneous interpretations. Seeking to address this limitation, researchers on the EU-funded NANOTESTS project propose to develop paper-based microfluidic detectors for the screening of drug-resistant bacteria.

Microfluidic devices based on paper are inexpensive to produce and can provide information on the toxicological impact of new drugs and chemicals on single bacteria. The activities of the project are focused on the identification of the appropriate surface chemistry for toxicological studies and on the development of microfluidic channels.

The long-term aim of the NANOTESTS study is to generate a microfluidic device that can perform multiplex toxicological evaluation of various drugs and gases. Using this system to evaluate the outcome of nanoparticle-based drug carriers is believed to produce robust solutions against antibiotic-resistant pathogens.