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Communication Dans Un Congrès Année : 2023

Functional characterisation of cysteine cathepsins as new virulence factors in the apicomplexan parasite Cryptosporidium parvum

Résumé

Cryptosporidium parvum is an apicomplexan parasite responsible for a zoonotic disease affecting both human health and livestock. The parasite is transmitted through the fecal-oral route and develops in ileal epithelial cells. The resulting enteric disease leads to watery diarrhoea that can be life-threatening in individuals with an immature or a compromised immune system. The only approved treatments against cryptosporidiosis have limited efficacy in the total clearance of the parasite. Improving our understanding of the parasite biology and host-pathogen interactions, as well as identifying new drug targets, are key steps towards the development of much needed effective control strategies. Cysteine proteases play key roles in the pathogenesis of protozoan parasites, including cell or tissue penetration, hydrolysis of host or parasite proteins, and evasion or modulation of the host immune response, making them attractive chemotherapeutic and vaccine targets. For instance, papain-like proteases (clan CA, family C1) from protozoan parasites responsible for human or bovine trypanosomiasis (cruzipain, congopain 1) and malaria (falcipains 2) are already well characterised as druggable targets based on in vitro and in vivo models. Genes encoding cathepsin L-like proteases (clan CA, family C1) have been reported in the genome of C. parvum, but only one (ie. cryptopain-1) has been analysed biochemically 3 to date. By combining our knowledge and expertise from the parasitology and protease biochemistry areas, we propose to detect cysteine protease-dependent activities throughout the C. parvum life cycle and characterise new cryptopain-like proteases in order to improve our understanding of their biological functions and identify novel targets for chemotherapy.
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Dates et versions

hal-04395670 , version 1 (15-01-2024)

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  • HAL Id : hal-04395670 , version 1

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Julie Tottey, Gilles Lalmanach. Functional characterisation of cysteine cathepsins as new virulence factors in the apicomplexan parasite Cryptosporidium parvum. Journées d'Animation Scientifique de la Fédération de Recherche en Infectiologie (FéRI), Fédération de Recherche en Infectiologie (FéRI), Jul 2023, Tours (France), France. ⟨hal-04395670⟩
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