The transcription factor Ndt80 is a repressor of Candida parapsilosis virulence attributes

Abstract

Candida parapsilosis is an emergent opportunistic yeast among hospital settings that affects mainly neonates and immunocompromised patients. Its most remarkable virulence traits are the ability to adhere to prosthetic materials, as well as the formation of biofilm on abiotic surfaces. The Ndt80 transcription factor was identified as one of the regulators of biofilm formation by C. parapsilosis; however, its function in this process was not yet clarified. By knocking out NDT80 (CPAR2-213640) gene, or even just one single copy of the gene, we observed substantial alterations of virulence attributes, including morphogenetic changes, adhesion and biofilm growth profiles. Both ndt80Δ and ndt80ΔΔ mutants changed colony and cell morphologies from smooth, yeast-shaped to crepe and pseudohyphal elongated forms, exhibiting promoted adherence to polystyrene microspheres and notably, forming a higher amount of biofilm compared to wild-type strain. Interestingly, we identified transcription factors Ume6, Cph2, Cwh41, Ace2, Bcr1, protein kinase Mkc1 and adhesin Als7 to be under Ndt80 negative regulation, partially explaining the phenotypes displayed by the ndt80ΔΔ mutant. Furthermore, ndt80ΔΔ pseudohyphae adhered more rapidly and were more resistant to murine macrophage attack, becoming deleterious to such cells after phagocytosis. Unexpectedly, our findings provide the first evidence for a direct role of Ndt80 as a repressor of C. parapsilosis virulence attributes. This finding shows that C. parapsilosis Ndt80 functionally diverges from its homolog in the close related fungal pathogen C. albicans.

Effects of fresh garlic extract on Candida albicans Sessile cells, biofilms and biofilm associated genes, Flo-8 and Ndt80

“…Presence of FGE might have triggered a stress response in C. albicans that led to the increased expression of Ndt80 to pump out potential threats. Aside from that, Ndt80 has been described to repress biofilm formation in Candida parapsilosis (Branco et al, 2021). Increase in the expression of Ndt80 in the present study could be a form of antibiofilm activity exerted by FGE.…”

The role of N-acetylcysteine on adhesion and biofilm formation of Candida parapsilosis isolated from catheter-related candidemia

“…All these factors require an extensive and complex regulatory network [26]. Genes such as BCR1, EFG1 and NDT80 have been shown to have an important role in biofilm development in C. parapsilosis, with one recent report identifying NDT80 as a repressor of C. parapsilosis virulence [26,27]. The current study therefore used qRT-PCR to detect the expression of adhesion-related genes (CpALS6 and CpALS7) and biofilm formation-related genes (CpEFG1 and CpBCR1) in C. parapsilosis after NAC intervention.…”

The Pathogenic Yeast Candida parapsilosis Forms Pseudohyphae through Different Signaling Pathways Depending on the Available Carbon Source

“…Similarly, in C. albicans , there is significant overlap between genes directly regulated by CaEfg1 and CaNdt80 ( 30 ). Surprisingly, in C. parapsilosis , Efg1 and Ndt80 have opposite effects on filamentous growth and biofilm formation, with Efg1 promoting and Ndt80 repressing this behavior ( 48 ). It is therefore possible that Ndt80 and Efg1 tune the extent of pseudohyphal growth, such that increased activity of one factor relative to the other could shift the population toward yeast or pseudohyphal forms.…”