Abstract
Candida albicans is a commensal of human mucosae, but also one of the most common fungal pathogens of humans. Systemic infections caused by this fungus, mostly affecting immunocompromised patients, are associated to fatality rates as high as 50% despite the available treatments. In order to improve this situation, it is necessary to fully understand how C. albicans is able to cause disease and how it copes with the host defenses. Our previous studies have revealed the importance of the C. albicans gene MBF1 in virulence and ability to colonize internal organs of mammalian and insect hosts. MBF1 encodes a putative transcriptional regulator, and as such it likely has an impact in the regulation of C. albicans gene expression during host infection. Here, recent advances in RNA-seq technologies were used to obtain a detailed analysis of the impact of MBF1 on C. albicans gene expression both in vitro and during infection. MBF1 was involved in the regulation of several genes with a role in glycolysis and response to stress, particularly to nutritional stress. We also investigated whether an interaction existed between MBF1 and GCN4, a master regulator of response to starvation, and found that both genes were needed for resistance to amino acid starvation, suggesting some level of interaction between the two. Reinforcing this idea, we showed that the proteins encoded by both genes could interact. Consistent with the role of MBF1 in virulence, we also established that GCN4 was necessary for virulence in the mouse model of systemic infection as well as in the Galleria mellonella infection model.
Highlights
Candida albicans is a fungal commensal of mucosae in the majority of humans, but it is an opportunistic pathogen
Strains were grown in the following media (when grown on solid media, 2% agar (Difco) was added): complete medium yeast extract peptone dextrose (YEPD): 1% Bacto peptone (Difco Laboratories, Basel, Switzerland), 0.5% Yeast extract (Difco) and 2% glucose (Fluka, Buchs, Switzerland); YEPD supplemented with 200 μg/ml nourseothricin (Werner BioAgents); minimal medium yeast nitrogen base (YNB): YNB (Difco) and 2% glucose (Fluka); YNB supplemented with complete supplement mixture (CSM) (MP Biomedicals); YNB supplemented with CSM without histidine (-his) (MP Biomedicals) with or without the addition of 3-Amino-1,2,4-triazole (3-AT) (Sigma) (1 to 5 mM, specified later in the text), YNB supplemented with histidine and leucine (YNB +his +leu) or with histidine only (YNB +his) and supplemented with cysteine and methionine
MBF1 was previously shown to be necessary for virulence of C. albicans in two models of systemic infection (AmorimVaz et al, 2015a), but its role was not yet understood
Summary
Candida albicans is a fungal commensal of mucosae in the majority of humans, but it is an opportunistic pathogen. It can cause mucosal infections or even invade bloodstream and internal organs if conditions are favorable. Examples of such conditions are immunosuppression of the host due to disease or medical treatments, or imbalance of the microbial flora associated for instance to the use of broad-spectrum antibiotics (Odds, 1988). Mucosal infections by C. albicans such as oral thrush or vulvovaginal candidiasis, not life-threatening, are associated to high morbidity. For the improvement of treatments, it is essential to better understand C. albicans biology and its interaction with the host
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
