| Popis: |
The polymorphous cellular shape of Candida albicans, in particular the transition from a yeast to a filamentous form, is crucial for either commensalism or life-threatening infections of the host. Various external or internal stimuli, including serum and nutrition starvation, have been shown to regulate filamentous growth primarily through two classical signaling pathways, the cAMP-PKA and the MAPK pathways. Genotoxic stress also induces filamentous growth, but through independent pathways, and little is known about negative regulation during this reversible morphological transition. In this study, we established that ARP1 in C. albicans, similar to its homolog in S. cerevisiae, has a role in nuclei separation and spindle orientation. Deletion of ARP1 generated filamentous and invasive growth as well as increased biofilm formation, accompanied by up-regulation of hyphae specific genes, such as HWP1, UME6 and ALS3. The filamentous and invasive growth of the ARP1 deletion strain was independent of transcription factors Efg1, Cph1 and Ume6, but was suppressed by deleting checkpoint BUB2 or overexpressing NRG1. Deletion of ARP1 impaired the colonization of Candida cells in mice and also attenuated virulence in a mouse model. All the data suggest that loss of ARP1 activates filamentous and invasive growth in vitro, and that it positively regulates virulence in vivo, which provides insight into actin-related morphology and pathogenicity in C. albicans. |
