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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. glabrata requires C. albicans for early infection.Mixed species oral infection with fluconazole resistant (CaFluR, CgFluR) and fluconazole sensitive (CaFluS) strains showed a significant reduction in number C. glabrata fluconazole resistant CgFluR cells (solid circles) following fluconazole treatment (despite being fluconazole resistant) that was proportional with reduction in fluconazole sensitive C. albicans CaFluS (open circles) CFUs (right). Tongue tissues were stained with Periodic acid-Schiff stain and viewed at 10X magnification (left). CaFluS and CgFluR infected mice showed normal tongue histology with a reduced fungal burden following fluconazole treatment, while CaFluR and CgFluR (yeast cells are shown in pink) infected mice showed typical hyphal invasion of the superficial epithelium with high fungal burden.
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ppat.1005522.g006: C. glabrata requires C. albicans for early infection.Mixed species oral infection with fluconazole resistant (CaFluR, CgFluR) and fluconazole sensitive (CaFluS) strains showed a significant reduction in number C. glabrata fluconazole resistant CgFluR cells (solid circles) following fluconazole treatment (despite being fluconazole resistant) that was proportional with reduction in fluconazole sensitive C. albicans CaFluS (open circles) CFUs (right). Tongue tissues were stained with Periodic acid-Schiff stain and viewed at 10X magnification (left). CaFluS and CgFluR infected mice showed normal tongue histology with a reduced fungal burden following fluconazole treatment, while CaFluR and CgFluR (yeast cells are shown in pink) infected mice showed typical hyphal invasion of the superficial epithelium with high fungal burden.

Mentions: To further confirm the requirement of C. albicans for C. glabrata for initial infection, we treated mice with fluconazole (Flu) after establishing mixed infection using Flu sensitive (CaFluS) or Flu resistant C. albicans (CaFluR) strains and Flu resistant C. glabrata (CgFluR) (Fig 6). Mice were treated with Flu for four days after an oral mixed infection was already established for four days. As expected, Flu treatment did not alter infection levels of either species in a mixed infection with CgFluR and CaFluR strains. However, for a mixed infection with C. glabrata CgFluR and C. albicans CaFluS strains, Flu treatment resulted in significant (by two logs, P<0.001) reduction of both C. glabrata and C. albicans. Flu treated animals infected with CaFluR strains in a mixed infection lost significantly (P<0.05) more weight (21.2 ± 0.2%) than mice infected with C. albicans CaFluS strains (18.9 ± 0.3%). Although we could not determine the co-locallization of C. albicans and C. glabrata histologically due to lack of fluorescent markers in Flu resistant strains, examination of tongues confirmed the reduction in superficial epithelial fungal burden and invasion upon Flu treatment (Fig 6). Thus, C. glabrata infection levels were proportional to those of C. albicans, showing that C. glabrata requires the presence of C. albicans for early infection in vivo.


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. glabrata requires C. albicans for early infection.Mixed species oral infection with fluconazole resistant (CaFluR, CgFluR) and fluconazole sensitive (CaFluS) strains showed a significant reduction in number C. glabrata fluconazole resistant CgFluR cells (solid circles) following fluconazole treatment (despite being fluconazole resistant) that was proportional with reduction in fluconazole sensitive C. albicans CaFluS (open circles) CFUs (right). Tongue tissues were stained with Periodic acid-Schiff stain and viewed at 10X magnification (left). CaFluS and CgFluR infected mice showed normal tongue histology with a reduced fungal burden following fluconazole treatment, while CaFluR and CgFluR (yeast cells are shown in pink) infected mice showed typical hyphal invasion of the superficial epithelium with high fungal burden.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814137&req=5

ppat.1005522.g006: C. glabrata requires C. albicans for early infection.Mixed species oral infection with fluconazole resistant (CaFluR, CgFluR) and fluconazole sensitive (CaFluS) strains showed a significant reduction in number C. glabrata fluconazole resistant CgFluR cells (solid circles) following fluconazole treatment (despite being fluconazole resistant) that was proportional with reduction in fluconazole sensitive C. albicans CaFluS (open circles) CFUs (right). Tongue tissues were stained with Periodic acid-Schiff stain and viewed at 10X magnification (left). CaFluS and CgFluR infected mice showed normal tongue histology with a reduced fungal burden following fluconazole treatment, while CaFluR and CgFluR (yeast cells are shown in pink) infected mice showed typical hyphal invasion of the superficial epithelium with high fungal burden.
Mentions: To further confirm the requirement of C. albicans for C. glabrata for initial infection, we treated mice with fluconazole (Flu) after establishing mixed infection using Flu sensitive (CaFluS) or Flu resistant C. albicans (CaFluR) strains and Flu resistant C. glabrata (CgFluR) (Fig 6). Mice were treated with Flu for four days after an oral mixed infection was already established for four days. As expected, Flu treatment did not alter infection levels of either species in a mixed infection with CgFluR and CaFluR strains. However, for a mixed infection with C. glabrata CgFluR and C. albicans CaFluS strains, Flu treatment resulted in significant (by two logs, P<0.001) reduction of both C. glabrata and C. albicans. Flu treated animals infected with CaFluR strains in a mixed infection lost significantly (P<0.05) more weight (21.2 ± 0.2%) than mice infected with C. albicans CaFluS strains (18.9 ± 0.3%). Although we could not determine the co-locallization of C. albicans and C. glabrata histologically due to lack of fluorescent markers in Flu resistant strains, examination of tongues confirmed the reduction in superficial epithelial fungal burden and invasion upon Flu treatment (Fig 6). Thus, C. glabrata infection levels were proportional to those of C. albicans, showing that C. glabrata requires the presence of C. albicans for early infection in vivo.

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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Related in: MedlinePlus