Abstract
Candida tropicalis is a pathogenic fungus that can cause opportunistic infections in humans. The ability of Candida species to transition between yeast and filamentous growth forms is essential to their ability to undergo environmental adaptation and to maintain virulence. In other fungal species, such as Candida albicans, N-acetylglucosamine (GlcNAc) can induce filamentous growth, whereas it suppresses such growth in C. tropicalis. In the present study, we found that knocking out the GlcNA-specific transporter gene NGT1 was sufficient to enhance C. tropicalis filamentous growth on Lee’s plus GlcNAc medium. This suggests that GlcNAc uptake into C. tropicalis cells is essential to the disruption of mycelial growth. As such, we further studied how GlcNAc catabolism-related genes were able to influence C. tropicalis filamentation. We found that HXK1 overexpression drove filamentous growth on Lee’s media containing glucose and GlcNAc, whereas the deletion of the same gene disrupted this filamentous growth. Interestingly, the deletion of the DAC1 or NAG1 genes impaired C. tropicalis growth on Lee’s plus GlcNAc plates. Overall, these results indicate that HXK1 can serve as a positive regulator of filamentous growth, with excess GlcNAc-6-PO4 accumulation being toxic to C. tropicalis. These findings may highlight novel therapeutic targets worthy of future investigation.
Highlights
Candida tropicalis is a fungal pathogen that can cause opportunistic infections in humans [1,2]
We sought to assess whether NGT1 is required in order for GlcNAc to suppress the filamentous growth of C. tropicalis by plating both WT and ngt1∆/∆ cells onto Lee’s agar plates containing either GlcNAc or glucose at 25 ◦C or 37 ◦C for 6 days, after which the morphology of the cells and colonies was assessed
We found that the cell growth rates of the dac1∆/∆+DAC1p-DAC1 and nag1∆/∆+NAG1p-NAG1 complemented strains were similar to those of the WT (Figure 6)
Summary
Candida tropicalis is a fungal pathogen that can cause opportunistic infections in humans [1,2]. Rising numbers of patients who are immunocompromised due to radiotherapy, chemotherapy, or organ transplantation have led to an increase in the incidence of opportunistic Candida infections [9,10]. While C. albicans is the most common cause of such fungal infections, C. tropicalis infection rates have been rapidly increasing among immunocompromised individuals, and these infections are associated with higher mortality rates [9,10,11]. C. tropicalis is more resistant to antifungal agents, such as fluconazole, when compared with C. albicans, with 15% of C. tropicalis isolates being fluconazole-resistant and just 3.8% C. albicans isolates being fluconazole-resistant [12,13] This suggests that C. tropicalis is an emerging pathogen worthy of closer study and medical scrutiny
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