Filamentous actinomycetes from hotspots of microbial diversity as sources of novel antibiotics

Antimicrobial resistance (AMR) in pathogenic bacteria represents a major global health crisis, calling for urgent action to combat it, including the discovery and development of novel chemical entities capable of addressing this ‘silent pandemic’. In this context, the research project ANTIDOTES aims at the discovery of new antibiotics through the bioprospecting of filamentous actinomycetes from specific microbial diversity hotspots, characterized by extreme conditions of varying nature, which force microorganisms to produce antibiotics and other bioactive metabolites as an adaptive response [1]. One area of focus is urban areas characterized by high anthropogenic impact, where the presence of chemical pollutants, heavy metals, and other contaminants creates a never-ending war for colonization. Another focus is marine microbial communities from Terra Nova Bay (Ross Sea, Antarctica), an extreme and still underexplored environment where microorganisms must develop unique physiological features to survive harsh and constantly shifting conditions, largely unaffected by human activities [2]. For both ecological niches, we have isolated a collection of filamentous actinomycetes, which have been morphologically de-replicated and are currently being fermented under a variety of cultivation conditions, both in liquid and solid media. The resulting library of extracts will be subjected to high-throughput screening against a panel of multidrug-resistant pathogens, followed by activity-guided purification of the bioactive molecules produced, along with their structural and biological characterization. Hopefully, our project will contribute in the identification of novel natural products to counteract the devastating effects of AMR. [1] Bisaccia et al. (2025). Antibiotics. 14:394. [2] Bisaccia et al. (2025). Environ. Microbiol. 27:e70045.