Project description:Candidozyma auris, previously known as Candida auris, is a recently found pathogenic yeast that causes systemic infections, showing a high mortality rate. Moreover, this species is highly resistant to the commonly used antifungal drugs and some of the strains are multiresistant. This fungus is also able to cause outbreaks in hospital settings. All of this has cause an alarm in the health care system. Therefore, finding alternative treatments for C. auris is critical. In this sense, our research group developed a monoclonal antibody (Ca37) against Candida albicans alcohol dehydrogenase enzyme (Adh) that successfully reduced the growth of the fungus in vitro and also showed a protective effect in vivo. Due to the high homology between both fungal alcohol dehydrogenases, we wanted to test the effect of Ca37 over C. auris. In order to do this, first we assessed if the monoclonal antibody also recognized C. auris Adh by sequencing the spots detected by two dimensional western blot when using the monoclonal antibody as first antibody. Two spots were detected in this western blot. The sequencing showed a mixture of proteins, but in both cases, Adh was one of the identified proteins.
Project description:Candida (Candidozyma) auris is an emerging multidrug-resistant fungal pathogen capable of establishing persistent skin colonization, contaminating the environment, and causing nosocomial outbreaks associated with high mortality rates. Conventional monotherapy frequently proves inadequate against biofilm-associated infections, underscoring the urgent need for novel therapeutic strategies. Therefore, we investigated the physiological and molecular responses of South Asian clade C. auris biofilms to treatment with a caspofungin–posaconazole combination. This regimen markedly reduced the median minimum inhibitory concentrations (4- to 32-fold for caspofungin; 8- to 64-fold for posaconazole) compared with monotherapies. Synergistic interactions were observed in all isolates, with fractional inhibitory concentration indices ranging from 0.078 to 0.31, and were further confirmed in vivo. Transcriptomic profiling revealed activation of multiple stress-response pathways, driving adaptive changes such as enhanced extracellular matrix production and biofilm-forming capacity, maintenance of intracellular cation homeostasis, osmotic stress response, and extensive cell wall and membrane remodeling affecting the mannan–glucan complex, chitin, sphingolipids, phosphatidylinositol- (4, 5)-bisphosphate, and ergosterol content. Additional responses included activation of RCT1 (fluconazole-inducible protein) and MDR1 (drug efflux pump), collectively promoting survival under combined antifungal pressure. These findings demonstrate the potent synergistic activity of caspofungin and posaconazole against C. auris biofilms, thereby supporting the development of effective combination therapies for this high-risk pathogen.