Leishmaniasis is a severe public health issue and the current treatments are toxic, costly or lead to parasite resistance, thus there is an urgent need for new drugs. The TEXLEISH consortium proposes a new paradigm: inhibiting host-parasite interactions, through targeting Leishmania exoproteome, in order to limit the risk of parasite resistance. TEXLEISH synergizes important expertise in medicinal chemistry, kinase-based drug discovery, parasite biology and in vivo testing to optimize CTN1122, a potent antileishmanial lead compound, into an orally active, safe, effective drug candidate. This process involves iterative rounds of chemical synthesis, assessment of its efficacy, toxicity, in vitro bioavailability, in vivo efficiency on animal models and the study of its mechanism of action. The TEXLEISH project will constitute a proof of concept to validate pathogen exoproteome as the future of target-based strategies.

Azole resistance in Aspergillus is one of the emerging public health concerns, listed as a WHO priority and suited to an integrated One Health approach. Selective pressure due to the use of azole pesticides in agriculture being incriminated, identification of clinical and environmental resistance patterns, and a greater understanding of the factors driving this resistance are urgently needed in order to issue recommendations to the stakeholders. The multidisciplinary AspergillusOne-health project strengthened with model and innovative methodologies (WGS, genotyping, MALDI typing, metabarcoding, AI) aims to identify hotspots as possible sources for selection of azole-resistance in the environment, after the detection of azole-resistant Aspergillus in patients and patiens's home, avian facilities, the environment (farming and sawmills), and detection of the azole fungicides in soil and air. The role of resistance trait on Aspergillus fitness cost will be investigated, using environmental strains and mutants selected after fungicide pressure, to assess its clinical involvement.