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Research Article

A novel allele of HWP1, isolated from a clinical strain of Candida albicans with defective hyphal growth and biofilm formation, has deletions of Gln/Pro and Ser/Thr repeats involved in cellular adhesion

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Pages 824-835 | Received 02 Jul 2008, Accepted 07 Dec 2008, Published online: 22 Dec 2009
 

Abstract

Gene HWP1 encodes a major Candida albicans hyphae cell wall protein which is a substrate of mammalian transglutaminases, promoting the cross-link of the fungus to epithelial cells. Here, we describe a novel HWP1 allele, isolated from C. albicans blood isolates. Analysis of the translated sequence shows that three important regions are absent in the novel allele, HWP1-2, relative to the previously described allele, HWP1-1. Regions 1 and 2 consist of 10 amino acid repeats important for functional conformation of peptide chains and attachment of C. albicans cells to the mammalian epithelia. Region 3 consists of 34 amino acid residues rich in threonine and serine, with O-glycosylation sites that promote the cross-linking with other proteins on C. albicans surface. The HWP1-2 homozygous strain L757 and the heterozygous strain L296 (HWP1-1/HWP1-2) have significantly lower levels of HWP1 expression during hyphal growth and biofilm formation compared to strain SC5314 (HWP1-1/HWP1-1). However, strain L296 properly forms hyphae and biofilms in vitro while strain L757 has reduced hyphal growth (40.4%) and biofilm formation (90.8%). Our results indicate that the HWP1 locus has biofilm specific allelic differential expression and suggest that the HWP1-2 encoded protein is less efficient to maintain cell-to-cell and cell-to-surface adhesion during biofilm formation. This is the first report of a natural variant of HWP1.

Acknowledgements

We thank Paloma Hernandez for technical assistance. A.C.B.P. received a PhD fellowship from Capes (Brazil); G.M.C. received a post-doctoral fellowship from FAPESP (Brazil) and A.L.C. and M.R.S.B. are supported by grants from FAPESP and CNPq (Brazil). M.R.S.B received an International Research Scholar grant from the Howard Hughes Medical Institute (USA).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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