Abstract
The hyphal wall protein 1 (HWP1) gene of Candida albicans encodes for a fungal cell wall protein, required for hyphal development and yeast adhesion to epithelial cells; yet, its role in pathogenesis remains largely unknown. In the present study, we analyzed two C. albicans laboratory strains, the DAY286 (HWP1/HWP1) and the null mutant FJS24 (hwp1/hwp1) and six clinical isolates [3 harbouring the homozygous HWP1 gene (HWP1/HWP1) and 3 the heterologous gene (HWP1/hwp1)]. Biofilm production, fungal HWP1 mRNA levels and ultrastructural morphology were investigated; also, the susceptibility of these strains to microglial cells was evaluated, in terms of fungal damage and immune cell-mediated secretory response. When comparing the two laboratory strains, biofilm was produced to a similar extent independently on the genetic background, while the susceptibility to microglial cell-mediated damage was higher in the hwp1/hwp1 mutant than in the HWP1/HWP1 counterpart. Also, transmission electron microscopy revealed differences between the two in terms of abundance in surface adhesin-like structures, fungal cell wall shape and intracellular granules. When comparing the clinical isolates grouped according to their HWP1 genotype, reduced biofilm production and increased susceptibility to microglial cell-mediated damage occurred in the HWP1/hwp1 isolates with respect to the HWP1/HWP1 counterparts; furthermore, upon exposure to microglial cells, the HWP1/HWP1 isolates, but not the HWP1/hwp1 counterpart, showed enhanced HWP1 mRNA levels. Finally, both laboratory and clinical isolates exhibited reduced ability to stimulate TNFα and nitric oxide production by microglial cells in the case of heterozygous or null mutant HWP1 genotype.Overall, these data indicate that C. albicans HWP1 genotype influences pathogen morphological structure as well as its interaction with microglial cells, while fungal biofilm production results unaffected, thus arguing on its role as virulence factor that directly affects host mediated defences.
Highlights
Candida albicans, a commensal of human mucosa in healthy people, behaves as an opportunistic pathogen in critical patients, where it causes deep-seated life-threatening infections [1]
When comparing the clinical isolates grouped according to their hyphal wall protein 1 (HWP1) genotype, reduced biofilm production and increased susceptibility to microglial cell-mediated damage occurred in the HWP1/hwp1 isolates with respect to the HWP1/HWP1 counterparts; upon exposure to microglial cells, the HWP1/HWP1 isolates, but not the HWP1/hwp1 counterpart, showed enhanced HWP1 mRNA levels
To assess the involvement of the HWP1 genotype on biofilm production, two widely described laboratory strains [13,16], the DAY286 and its hwp1/hwp1 mutant (FJS24), were investigated according to the protocols described in Materials and methods
Summary
A commensal of human mucosa in healthy people, behaves as an opportunistic pathogen in critical patients, where it causes deep-seated life-threatening infections [1]. Invasive candidiasis (IC) affects 9% of patients in the intensive care units and 2e20% of preterm newborns, with a mortality ranging from 20 to 50% [2,3]. Medical devices, such as cardiovascular and urinary catheters, dialysis access and ventriculoperitoneal shunts are considered to be a crucial point of entry for Candida in these clinical settings [4e6], where, though relatively rare, meningoencephalitis may occur as a severe complication of deep-seated candidiasis [2,3,7].
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