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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 enhances C. glabrata colonization in murine oropharyngeal candidiasis model.(A) Colony Forming Units (CFU) per gram of tongue tissues were recovered from infections with C. albicans alone, C. glabrata alone or C. albicans and C. glabrata co-infected mice after 5 days. C. glabrata colonization increased by one log-fold upon co-infection with C. albicans. (B) Pre-establishing C. albicans infection (24 h or 48 h before C. glabrata infection) further increased subsequent C. glabrata colonization by two log-fold in mice tongue tissues. Differences between groups were analyzed by a student’s t test (**P<0.003, **P<0.001, ***P<0.0001). (C) C. glabrata infection alone did not result in mice weight loss, however the rate of weight loss was accelerated in the mixed infection (red arrow indicates initiation of C. glabrata infection). Animal weights (mean and SD of each group, n = 7) are shown for each group (black, C. glabrata infection only; blue C. albicans infection only; red, C. albicans infection for 48 h followed by C. glabrata infection).
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ppat.1005522.g004: C. albicans enhances C. glabrata colonization in murine oropharyngeal candidiasis model.(A) Colony Forming Units (CFU) per gram of tongue tissues were recovered from infections with C. albicans alone, C. glabrata alone or C. albicans and C. glabrata co-infected mice after 5 days. C. glabrata colonization increased by one log-fold upon co-infection with C. albicans. (B) Pre-establishing C. albicans infection (24 h or 48 h before C. glabrata infection) further increased subsequent C. glabrata colonization by two log-fold in mice tongue tissues. Differences between groups were analyzed by a student’s t test (**P<0.003, **P<0.001, ***P<0.0001). (C) C. glabrata infection alone did not result in mice weight loss, however the rate of weight loss was accelerated in the mixed infection (red arrow indicates initiation of C. glabrata infection). Animal weights (mean and SD of each group, n = 7) are shown for each group (black, C. glabrata infection only; blue C. albicans infection only; red, C. albicans infection for 48 h followed by C. glabrata infection).

Mentions: To determine whether our observed binding between C. albicans and C. glabrata has relevance in vivo, we examined the ability of C. glabrata to establish infection in our murine model of OPC. Since C. glabrata has not been used before in OPC infection models, we began with a single species oral infection of C57BL/6 mice with C. glabrata alone as we have previously done with C. albicans (Fig 4A). In this model, sublingual infection with a C. albicans inoculum of 1 X 106 cells/ml typically produces clinical symptoms and white tongue plaques 4–5 days post infection, and recovery of 1 X 107 CFU / gm tongue tissue at 5 days post infection. Surprisingly, in no infection experiments using C. glabrata did we observe the typical appearance of white tongue plaques indicative of clinical infection. We tried varying immunosuppressive agents (triampicinolone acetonide, cyclophosphamide), mouse strains (BALB/c, IL17RAk/o) and used inocula size of C. glabrata ranging from 1 X 107 to 1 X 1010 cells/ml. In all cases, infection with C. glabrata alone resulted in no clinical appearance of disease or weight loss in animals. Consistent with this lack of disease, the recoverable C. glabrata CFUs from the tongue were extremely low (4–7 X 102 CFU/g of tongue tissue).


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 enhances C. glabrata colonization in murine oropharyngeal candidiasis model.(A) Colony Forming Units (CFU) per gram of tongue tissues were recovered from infections with C. albicans alone, C. glabrata alone or C. albicans and C. glabrata co-infected mice after 5 days. C. glabrata colonization increased by one log-fold upon co-infection with C. albicans. (B) Pre-establishing C. albicans infection (24 h or 48 h before C. glabrata infection) further increased subsequent C. glabrata colonization by two log-fold in mice tongue tissues. Differences between groups were analyzed by a student’s t test (**P<0.003, **P<0.001, ***P<0.0001). (C) C. glabrata infection alone did not result in mice weight loss, however the rate of weight loss was accelerated in the mixed infection (red arrow indicates initiation of C. glabrata infection). Animal weights (mean and SD of each group, n = 7) are shown for each group (black, C. glabrata infection only; blue C. albicans infection only; red, C. albicans infection for 48 h followed by C. glabrata infection).
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ppat.1005522.g004: C. albicans enhances C. glabrata colonization in murine oropharyngeal candidiasis model.(A) Colony Forming Units (CFU) per gram of tongue tissues were recovered from infections with C. albicans alone, C. glabrata alone or C. albicans and C. glabrata co-infected mice after 5 days. C. glabrata colonization increased by one log-fold upon co-infection with C. albicans. (B) Pre-establishing C. albicans infection (24 h or 48 h before C. glabrata infection) further increased subsequent C. glabrata colonization by two log-fold in mice tongue tissues. Differences between groups were analyzed by a student’s t test (**P<0.003, **P<0.001, ***P<0.0001). (C) C. glabrata infection alone did not result in mice weight loss, however the rate of weight loss was accelerated in the mixed infection (red arrow indicates initiation of C. glabrata infection). Animal weights (mean and SD of each group, n = 7) are shown for each group (black, C. glabrata infection only; blue C. albicans infection only; red, C. albicans infection for 48 h followed by C. glabrata infection).
Mentions: To determine whether our observed binding between C. albicans and C. glabrata has relevance in vivo, we examined the ability of C. glabrata to establish infection in our murine model of OPC. Since C. glabrata has not been used before in OPC infection models, we began with a single species oral infection of C57BL/6 mice with C. glabrata alone as we have previously done with C. albicans (Fig 4A). In this model, sublingual infection with a C. albicans inoculum of 1 X 106 cells/ml typically produces clinical symptoms and white tongue plaques 4–5 days post infection, and recovery of 1 X 107 CFU / gm tongue tissue at 5 days post infection. Surprisingly, in no infection experiments using C. glabrata did we observe the typical appearance of white tongue plaques indicative of clinical infection. We tried varying immunosuppressive agents (triampicinolone acetonide, cyclophosphamide), mouse strains (BALB/c, IL17RAk/o) and used inocula size of C. glabrata ranging from 1 X 107 to 1 X 1010 cells/ml. In all cases, infection with C. glabrata alone resulted in no clinical appearance of disease or weight loss in animals. Consistent with this lack of disease, the recoverable C. glabrata CFUs from the tongue were extremely low (4–7 X 102 CFU/g of tongue tissue).

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