Comparative transcriptomic analysis of the response of CUG-clade Candida species to phagocytosis
Pathogenic Candida fungi are a leading cause of opportunistic, hospital-associated bloodstream infections with high mortality rates, typically in immunocompromised patients. Several species, including C. albicans, the most prevalent cause of infection, belong to the monophyletic CUG clade of yeasts. Much is known about the interaction of C. albicans with innate immune cells, which are crucial for controlling infection. Phagocytosis of C. albicans elicits transcriptional induction of several pathways involved in catabolism of non-glucose carbon sources that are important for virulence, termed alternative carbon metabolism. However, the response of other CUG clade species has not been characterized. Here, we analyzed the transcriptional responses to macrophage phagocytosis by seven Candida species across a range of virulence and clinical importance. We observed a strikingly high degree of conservation even in species that rarely cause infection and defined a core induced response linked to alternative carbon metabolism. Many of these genes showed convergence to the same level of expression upon phagocytosis. Some differences were observed, however, including notably deficient expression of heat shock protein HSP21 in common pathogen C. parapsilosis that may be linked to reduced thermotolerance in this species. In contrast, C. parapsilosis showed a more robust induction of metabolite transporters compared to the related L. elongisporus, which rarely causes infection. This study significantly broadens our understanding of host interactions in CUG clade species and shows that while metabolic plasticity is an important attribute in pathogenic Candida species, it is neither an adaptation to, nor sufficient for, virulence. Overall design: The transcriptional responses of six Candida species (C. albicans, C. dubliniensis, C. tropicalis, C. parapsilosis, Lodderomyces elongisporus and Clavispora lusitaniae) to phagocytosis was analysed by incubating fungal cells in mammalian medium in the presence or absence of primary macrophages for 1 hour, followed by RNA extraction and sequencing. This experiment was performed in duplicate.