The AntiGlyDisco operation explores new scientific solutions to combat bacterial resistance to antibiotics.
A new scientific operation carried out by i3S – Institute for Research and Innovation in Health at the University of Porto, and co-financed by the COMPETE 2030 programme, is exploring an innovative way to combat the growing threat of antibiotic resistance. The AntiGlyDisco operation proposes a paradigm shift: instead of trying to kill bacteria directly, as traditional antibiotics do, it aims to make them less dangerous and more vulnerable to existing treatments.
‘The research project proposed under the Compete 2030 call is a direct response to the growing threat posed by antibiotic resistance, a pressing challenge that jeopardises global public health,’ says Didier Cabanes, head of the AntiGlyDisco operation and leader of the Molecular Microbiology group at i3S. “In recent years, the emergence of multi-resistant bacterial strains, associated with factors such as globalisation, climate change and the excessive use of antibiotics, has created a crisis with significant human suffering, economic losses and the degradation of health systems around the world.”
The focus of the work is on a structure present on the surface of many dangerous bacteria — called wall teichoic acids (WTA) — which, when decorated with sugars, help bacteria escape the immune system and resist antibiotics. This ‘decoration’ is done by specific enzymes, and by inhibiting these enzymes, it is possible to reduce the bacteria’s ability to cause serious infections, while facilitating the action of existing antibiotics.
In this context, the i3S team is studying an enzyme called RmlT, which is essential for the addition of certain sugars to the WTAs of the bacterium Listeria monocytogenes, one of the most dangerous food pathogens in Europe. Although not vital for the growth of the bacterium, this enzyme is crucial for its virulence — that is, its ability to cause disease. This makes RmlT a promising target for the development of drugs that stop infection without exerting selective pressure that could lead to resistance.
The AntiGlyDisco operation combines several cutting-edge techniques, from resolving the enzyme’s 3D structure to computational modelling and screening millions of chemical compounds with the potential to inhibit it. The most promising compounds will be tested in laboratory assays and animal models to assess their efficacy, safety and real impact on infection.
In addition, the researchers aim to understand how the bacterium alters its surface structure throughout an infection, an important aspect to ensure that the inhibitors developed remain effective at different stages of the disease.
‘Given this scenario, the proposed project aims to respond to the urgent need for innovative therapeutic strategies to combat bacterial infections,’ adds Didier Cabanes. ‘Instead of targeting bacterial growth and replication like traditional antibiotics, the project seeks to explore alternative approaches specifically targeting bacterial wall-modifying enzymes involved in virulence and antibiotic resistance.’
One of the great advantages of this approach is that it acts without directly affecting bacterial growth. This means that treatments derived from this research are less likely to promote the emergence of new resistances, in addition to preserving the microbiota — the set of beneficial bacteria present in the human body.
The impact of the operation could extend beyond Listeria monocytogenes, as the RmlT enzyme shares similarities with enzymes from other dangerous bacteria, such as Staphylococcus or Enterococcus. The ultimate goal is to create a new generation of drugs that not only reduce the infectivity of bacteria but also improve the effectiveness of existing antibiotics.
“Compete 2030 funding should enable the development of new antibacterial inhibitors, contributing significantly to scientific knowledge, healthcare provision and social well-being,” concludes Didier Cabanes.
With a multidisciplinary and collaborative approach, the AntiGlyDisco operation is at the forefront of the fight against antimicrobial resistance — one of the greatest threats to global public health — and is aligned with the Sustainable Development Goals of the 2030 Agenda, particularly with regard to promoting health and well-being and scientific innovation at the service of society.
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