An international study co-ordinated by the Interdisciplinary Centre of Nanoscience of Marseille, with the collaboration of organisations and research centres of excellence, including the Biology and Nanotechnology Laboratory of the Department of Engineering and Architecture at the University of Trieste, has synthesised a new antibacterial compound that promises to be an excellent candidate for the fight against antibiotic resistance, a growing global public health problem that still causes millions of deaths worldwide.

‘The main threat is posed by the eskape group of bacteria - comprising the genera Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species - because they are particularly virulent and resistant to antibiotics introduced with treatment” explains Sabrina Pricl, one of the study's researchers and associate professor of chemical engineering at the Department of Engineering and Architecture at the University of Trieste. “Hence the need to develop new antibacterial agents that, on the one hand, are able to kill bacteria, on the other, are not toxic to the organisms that take them in and, above all, do not induce the appearance of further drug resistance.’

The molecule synthesised by the researchers - an amphiphilic dendrimer called AD1b - proved highly efficient against all Gram-negative bacteria, including drug-resistant strains such as Escherichia coli and Acinetobacter baumannii.

The compound interacts with the bacterium by an innovative mechanism of action: it binds to the phospholipids of the bacterial membrane, such as phosphatidylglycerol and cardiolipin, causing the destruction of the membrane itself and the consequent collapse of cell metabolism, leading to the death of the bacterium, without damaging healthy cells - even in vivo - and minimising the risk of developing new resistance, a problem that otherwise plagues traditional antibiotics.

In preclinical tests, the molecule demonstrated strong antibacterial activity as well as great safety, with very low toxicity and no haemolytic effect - results later confirmed in in vivo tests. Moreover, after thirty days of exposure to the compound, no resistance was observed; on the contrary, a drastic reduction in the bacterial load in infected animals was observed.

‘This molecule could pave the way for safer and more targeted therapies and thus give an impetus to the treatment of resistant infections: together with its efficacy, in fact, the ability to not induce resistance puts it in pole position to be further developed at the clinical translational level’ explains Professor Sabrina Pricl.

Researchers from the University of Trieste worked on the design of the AD1 molecule and took part in the computational study, using molecular dynamics simulations to study the interaction between AD1b and the bacterial membrane, applying advanced methodologies supported by CINECA's supercomputing resources.

The research project was funded with NRRP funds and was supported by ICSC, the National Research Centre in High-Performance Computing, Big Data and Quantum Computing.