Investigation of the Candida–host interaction using dual RNA-seq

Candida species are commensal yeasts but are also responsible of life-threatening infection in at-risk populations, like new-born or immunocompromised patients. Candida albicans is the most common causative species, and the most studied. Moreover, non- albicans Candida species as Candida glabrata , Candida parapsilosis and Candida tropicalis cause a large proportion of infections. In our study we investigated the interaction between four Candida species and human vaginal epithelial cells A431 by using a dual RNA-seq method. Our aim is to identify the different transcriptomic response of each yeast, and of the host, during the infection of human cells. Gene Ontology analysis of up-regulated genes in the yeasts during infection implicated the ergosterol (ERG) pathway in C. parapsilosis only. We therefore investigated the role of the ERG pathway in the three Candida species in which it is currently possible to generate gene knockouts. The transcriptional factor Upc2 is the main regulator of ERG gene expression in C. albicans and C. parapsilosis . C. glabrata has two UPC2 orthologs, called CgUPC2A and CgUPC2B. We found that deleting CgUPC2A or CgUPC2B or both together does not reduce the damage inflicted by C. glabrata on host cells. However, deleting UPC2in C. albicans greatly reduces damage. Deleting UPC2 in C. parapsilosis appears to reduce damage of host cells; however further investigation is required. Our results show the that the role of ergosterol pathway in the host pathogen interaction differs between Candida species.