Study of the effect of candida albicans recombinant proteins and derived monoclonal antibodies on protumoral processes and as diagnostic and therapeutic tools

Résumé

Candida albicans is a human commensal yeast that can sometimes cause life-threatening infections, especially in immunocompromised patients. The high mortality rates associated with this fungus make necessary the study of new diagnostic techniques and alternative therapies. In this PhD thesis, five proteins of the yeast (Adh1, Eno1, Ilv5, Kre9 and Qcr2) were produced as recombinant proteins, which showed ability to stimulate the hepatic endothelial cells, leading to an increase in tumor cell adhesion. Monoclonal antibodies against two of those proteins, Adh1 and Kre9, were also generated and tested against C. albicans. Those antibodies were able to reduce the C. albicans stimulatory effect on hepatic endothelial cells, reducing the tumor cell adhesion. On the other hand, one of the antibodies, anti-Kre9, showed ability to differentiate C. albicans from Candida dubliniensis and clinically relevant filamentous fungi. The other antibody, anti-Adh1, showed ability to effectively reduce yeast growth in vitro, to reduce the necessary antifungal dose to inhibit the fungus, and to increase survival in a Galleria mellonella animal infection model. The data presented here point out Adh1 and Kre9 proteins as relevant new candidates to be diagnostic and/or treatment targets to improve the outcome of patients suffering from C. albicans infections.