SR-Like RNA-Binding Protein Slr1 Affects Candida albicans Filamentation and Virulence
Year: 2013
Type: article
Abstract: Candida albicans causes both mucosal and disseminated infections, and its capacity to grow as both yeast and hyphae is a key virulence factor. Hyphal formation is a type of polarized growth, and members of the SR (serine-arginine) family of RNA-binding proteins influence polarized growth of both Saccharomyces cerevisiae and Aspergillus nidulans. Therefore, we investigated whether SR-like proteins affect filamentous growth and virulence of C. albicans. BLAST searches with S. cerevisiae SR-like protein Npl3 (ScNpl3) identified two C. albicans proteins: CaNpl3, an apparent ScNpl3 ortholog, and Slr1, another SR-like RNA-binding protein with no close S. cerevisiae ortholog. Whereas ScNpl3 was critical for growth, deletion of NPL3 in C. albicans resulted in few phenotypic changes. In contrast, the slr1Δ/Δ mutant had a reduced growth rate in vitro, decreased filamentation, and impaired capacity to damage epithelial and endothelial cells in vitro. Mice infected intravenously with the slr1Δ/Δ mutant strain had significantly prolonged survival compared to that of mice infected with the wild-type or slr1Δ/Δ mutant complemented with SLR1 (slr1Δ/Δ+SLR1) strain, without a concomitant decrease in kidney fungal burden. Histopathology, however, revealed differential localization of slr1Δ/Δ hyphal and yeast morphologies within the kidney. Mice infected with slr1Δ/Δ cells also had an increased brain fungal burden, which correlated with increased invasion of brain, but not umbilical vein, endothelial cells in vitro. The enhanced brain endothelial cell invasion was likely due to the increased surface exposure of the Als3 adhesin on slr1Δ/Δ cells. Our results indicate that Slr1 is an SR-like protein that influences C. albicans growth, filamentation, host cell interactions, and virulence.
Source: Infection and Immunity
DOI: 10.1128/iai.00864-12
Authors: Chaiyaboot Ariyachet, Norma V. Solis, Yaoping Liu, Nemani V. Prasadarao, Scott G. Filler, Anne E. McBride
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Howard Hughes Medical Institute, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research, National Center for Research Resources, National Center for Advancing Translational Sciences, Clinical and Translational Science Institute, University of California, Los Angeles
Awards: UCLA Clinical and Translational Science Institute, G2171327356, G2279601244, G2430628023, PATHOGENESIS OF OROPHARYNGEAL CANDIDIASIS, G2663518188, UCLA Clinical and Translational Science Institute, G351251752, Comparative Functional Genomics INBRE in Maine, Candida albicans Epithelial Cell Interactions and Oropharyngeal Disease, G3649265139, G5737857746, G634933097
OpenAlex ID: W2124306464