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Candida glabrata Binding to Candida albicans Hyphae Enables Its Development in Oropharyngeal Candidiasis.

Tati S, Davidow P, McCall A, Hwang-Wong E, Rojas IG, Cormack B, Edgerton M - PLoS Pathog. (2016)

Bottom Line: Furthermore, C. glabrata required C. albicans for colonization of tongues, since decreasing C. albicans burden with fluconazole also reduced C. glabrata.C. albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion of C. glabrata and to establish OPC.C. glabrata cell wall protein coding genes EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to C. albicans hyphae and remarkably, their expression was induced by incubation with germinated C. albicans.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, United States of America.

ABSTRACT
Pathogenic mechanisms of Candida glabrata in oral candidiasis, especially because of its inability to form hyphae, are understudied. Since both Candida albicans and C. glabrata are frequently co-isolated in oropharyngeal candidiasis (OPC), we examined their co-adhesion in vitro and observed adhesion of C. glabrata only to C. albicans hyphae microscopically. Mice were infected sublingually with C. albicans or C. glabrata individually, or with both species concurrently, to study their ability to cause OPC. Infection with C. glabrata alone resulted in negligible infection of tongues; however, colonization by C. glabrata was increased by co-infection or a pre-established infection with C. albicans. Furthermore, C. glabrata required C. albicans for colonization of tongues, since decreasing C. albicans burden with fluconazole also reduced C. glabrata. C. albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion of C. glabrata and to establish OPC. C. glabrata cell wall protein coding genes EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to C. albicans hyphae and remarkably, their expression was induced by incubation with germinated C. albicans. Thus, we found a near essential requirement for the presence of C. albicans for both initial colonization and establishment of OPC infection by C. glabrata.

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C. albicans and C. glabrata are co-localized and both invade murine tongue tissues in a mixed infection.(A, B and C) PAS stained formalin-fixed and paraffin embedded sections (5 μm) from tongues of mixed C. albicans and C. glabrata infection at day 5 showed widespread fungal plaques and hyphal invasion (yeast are stained magenta) of superficial epithelium (box) and underlying epithelium (arrows). Dark blue cells are neutrophils, lighter blue cells are tongue epithelia. Magnification is 10x. (B) 40x and (C) 100x magnification show C. albicans hyphae with associated yeast cells within the mucosa. (D, E and F) Immunofluorescent and DIC merged images of C. albicans (red) and C. glabrata (green) from tongues at day 5 post-infection. (D) Arrowheads show hyphae penetration into the epithelium. (E and F) Arrowheads at left indicate C. glabrata in contact with hyphae, while other C. glabrata are within epithelium unassociated with C. albicans hyphae (E, lower arrow). Scale bars represent, in order (A-F), 50, 10, 5, 50, 10, and 10 μm.
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ppat.1005522.g005: C. albicans and C. glabrata are co-localized and both invade murine tongue tissues in a mixed infection.(A, B and C) PAS stained formalin-fixed and paraffin embedded sections (5 μm) from tongues of mixed C. albicans and C. glabrata infection at day 5 showed widespread fungal plaques and hyphal invasion (yeast are stained magenta) of superficial epithelium (box) and underlying epithelium (arrows). Dark blue cells are neutrophils, lighter blue cells are tongue epithelia. Magnification is 10x. (B) 40x and (C) 100x magnification show C. albicans hyphae with associated yeast cells within the mucosa. (D, E and F) Immunofluorescent and DIC merged images of C. albicans (red) and C. glabrata (green) from tongues at day 5 post-infection. (D) Arrowheads show hyphae penetration into the epithelium. (E and F) Arrowheads at left indicate C. glabrata in contact with hyphae, while other C. glabrata are within epithelium unassociated with C. albicans hyphae (E, lower arrow). Scale bars represent, in order (A-F), 50, 10, 5, 50, 10, and 10 μm.

Mentions: Next, we examined tongues of mixed-infected mice histologically to determine whether C. glabrata alters C. albicans invasive properties and to identify the localization of C. glabrata infection within the mucosal epithelium. For these experiments we infected mice with fluorescent-tagged strains of C. albicans (CAF2-yCherry) on day 0 and C. glabrata (CgVSY55) on day 2; and collected tongue tissues on day 5. Tongues were sectioned and stained with either PAS to visualize fungal-tissue architecture or cryo-sectioned for visualization of yeast cell localization by fluorescence microscopy. Tongues from mice with mixed infection showed robust fungal plaque formation as well as extensive C. albicans hyphal penetration of the superficial epithelium (Fig 5A, boxed region) as well as invasion into some regions of the underlying epithelium and lamina propria (Fig 5A, arrows). Closer inspection of these regions showed widespread C. albicans hyphae; and in some areas yeast cells were observed both adherent to hyphae and as unattached cells that were likely to be C. glabrata (Fig 5B and 5C, arrows). Fluorescent imaging of these regions confirmed that the majority of tissue invasion was with C. albicans hyphae (Fig 5D, boxed region, red), however C. glabrata cells (green) were also observed within these tissues both associated with C. albicans hyphae as well as being unconnected and separate within the epithelium (Fig 5E and 5F, arrows). In contrast, mono-species C. glabrata infection resulted on only very small superficial plaques that were localized on the surface mucosa without any invasion. Thus, infection of oral epithelium with C. albicans and the presence of its hyphae were permissive for infection and tissue invasion by C. glabrata.


Candida glabrata Binding to Candida albicans Hyphae Enables Its Development in Oropharyngeal Candidiasis.

Tati S, Davidow P, McCall A, Hwang-Wong E, Rojas IG, Cormack B, Edgerton M - PLoS Pathog. (2016)

C. albicans and C. glabrata are co-localized and both invade murine tongue tissues in a mixed infection.(A, B and C) PAS stained formalin-fixed and paraffin embedded sections (5 μm) from tongues of mixed C. albicans and C. glabrata infection at day 5 showed widespread fungal plaques and hyphal invasion (yeast are stained magenta) of superficial epithelium (box) and underlying epithelium (arrows). Dark blue cells are neutrophils, lighter blue cells are tongue epithelia. Magnification is 10x. (B) 40x and (C) 100x magnification show C. albicans hyphae with associated yeast cells within the mucosa. (D, E and F) Immunofluorescent and DIC merged images of C. albicans (red) and C. glabrata (green) from tongues at day 5 post-infection. (D) Arrowheads show hyphae penetration into the epithelium. (E and F) Arrowheads at left indicate C. glabrata in contact with hyphae, while other C. glabrata are within epithelium unassociated with C. albicans hyphae (E, lower arrow). Scale bars represent, in order (A-F), 50, 10, 5, 50, 10, and 10 μm.
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Related In: Results  -  Collection

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ppat.1005522.g005: C. albicans and C. glabrata are co-localized and both invade murine tongue tissues in a mixed infection.(A, B and C) PAS stained formalin-fixed and paraffin embedded sections (5 μm) from tongues of mixed C. albicans and C. glabrata infection at day 5 showed widespread fungal plaques and hyphal invasion (yeast are stained magenta) of superficial epithelium (box) and underlying epithelium (arrows). Dark blue cells are neutrophils, lighter blue cells are tongue epithelia. Magnification is 10x. (B) 40x and (C) 100x magnification show C. albicans hyphae with associated yeast cells within the mucosa. (D, E and F) Immunofluorescent and DIC merged images of C. albicans (red) and C. glabrata (green) from tongues at day 5 post-infection. (D) Arrowheads show hyphae penetration into the epithelium. (E and F) Arrowheads at left indicate C. glabrata in contact with hyphae, while other C. glabrata are within epithelium unassociated with C. albicans hyphae (E, lower arrow). Scale bars represent, in order (A-F), 50, 10, 5, 50, 10, and 10 μm.
Mentions: Next, we examined tongues of mixed-infected mice histologically to determine whether C. glabrata alters C. albicans invasive properties and to identify the localization of C. glabrata infection within the mucosal epithelium. For these experiments we infected mice with fluorescent-tagged strains of C. albicans (CAF2-yCherry) on day 0 and C. glabrata (CgVSY55) on day 2; and collected tongue tissues on day 5. Tongues were sectioned and stained with either PAS to visualize fungal-tissue architecture or cryo-sectioned for visualization of yeast cell localization by fluorescence microscopy. Tongues from mice with mixed infection showed robust fungal plaque formation as well as extensive C. albicans hyphal penetration of the superficial epithelium (Fig 5A, boxed region) as well as invasion into some regions of the underlying epithelium and lamina propria (Fig 5A, arrows). Closer inspection of these regions showed widespread C. albicans hyphae; and in some areas yeast cells were observed both adherent to hyphae and as unattached cells that were likely to be C. glabrata (Fig 5B and 5C, arrows). Fluorescent imaging of these regions confirmed that the majority of tissue invasion was with C. albicans hyphae (Fig 5D, boxed region, red), however C. glabrata cells (green) were also observed within these tissues both associated with C. albicans hyphae as well as being unconnected and separate within the epithelium (Fig 5E and 5F, arrows). In contrast, mono-species C. glabrata infection resulted on only very small superficial plaques that were localized on the surface mucosa without any invasion. Thus, infection of oral epithelium with C. albicans and the presence of its hyphae were permissive for infection and tissue invasion by C. glabrata.

Bottom Line: Furthermore, C. glabrata required C. albicans for colonization of tongues, since decreasing C. albicans burden with fluconazole also reduced C. glabrata.C. albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion of C. glabrata and to establish OPC.C. glabrata cell wall protein coding genes EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to C. albicans hyphae and remarkably, their expression was induced by incubation with germinated C. albicans.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, United States of America.

ABSTRACT
Pathogenic mechanisms of Candida glabrata in oral candidiasis, especially because of its inability to form hyphae, are understudied. Since both Candida albicans and C. glabrata are frequently co-isolated in oropharyngeal candidiasis (OPC), we examined their co-adhesion in vitro and observed adhesion of C. glabrata only to C. albicans hyphae microscopically. Mice were infected sublingually with C. albicans or C. glabrata individually, or with both species concurrently, to study their ability to cause OPC. Infection with C. glabrata alone resulted in negligible infection of tongues; however, colonization by C. glabrata was increased by co-infection or a pre-established infection with C. albicans. Furthermore, C. glabrata required C. albicans for colonization of tongues, since decreasing C. albicans burden with fluconazole also reduced C. glabrata. C. albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion of C. glabrata and to establish OPC. C. glabrata cell wall protein coding genes EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to C. albicans hyphae and remarkably, their expression was induced by incubation with germinated C. albicans. Thus, we found a near essential requirement for the presence of C. albicans for both initial colonization and establishment of OPC infection by C. glabrata.

Show MeSH
Related in: MedlinePlus