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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 Als3 and Als1 hyphal cell wall adhesins are involved in C. glabrata adherence to C. albicans hyphae.(A) C. glabrata (CgVSY55) adherence to C. albicans Als1, Als3 and Als1/3 deficient strains was measured using fluorescent microscopy. C. glabrata showed a significant (**P<0.001,***P<0.0006) decrease in adherence to C. albicans hyphae of als3Δ/Δ, als1Δ/Δ, and als1/als3Δ/Δ mutants; while C. albicans Als1 and Als3 complementation strains had restored adherence. (B) S. cerevisiae strains expressing C. albicans Als1 and Als3 adhesins and an empty vector (control) were incubated with CgVSY55 and their adherence was quantifed by direct visualization. Both Als1 and Als3 expressing S. cerevisiae strains had a significant (***P<0.001) increase in Binding Index compared to control empty vector. Differences between groups were analyzed by a student’s t test.
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ppat.1005522.g003: C. albicans Als3 and Als1 hyphal cell wall adhesins are involved in C. glabrata adherence to C. albicans hyphae.(A) C. glabrata (CgVSY55) adherence to C. albicans Als1, Als3 and Als1/3 deficient strains was measured using fluorescent microscopy. C. glabrata showed a significant (**P<0.001,***P<0.0006) decrease in adherence to C. albicans hyphae of als3Δ/Δ, als1Δ/Δ, and als1/als3Δ/Δ mutants; while C. albicans Als1 and Als3 complementation strains had restored adherence. (B) S. cerevisiae strains expressing C. albicans Als1 and Als3 adhesins and an empty vector (control) were incubated with CgVSY55 and their adherence was quantifed by direct visualization. Both Als1 and Als3 expressing S. cerevisiae strains had a significant (***P<0.001) increase in Binding Index compared to control empty vector. Differences between groups were analyzed by a student’s t test.

Mentions: We hypothesized that C. glabrata might bind C. albicans cell wall proteins directly. To test candidate C. albicans hyphal wall adhesins required for C. glabrata adhesion, we performed co-adhesion assays with ALS1 and ALS3 deficient C. albicans (Fig 3). We found that C. glabrata had significantly decreased adherence to hyphae of a C. albicans als3Δ/Δ mutant (72.3% reduction), an als1Δ/Δ mutant (28.8% reduction), and an als1/als3Δ/Δ double mutant (86% reduction). ALS1 and ALS3 complementation strains showed restoration of adherence to levels closer to that of wild type strain (Fig 3A). To further validate the role of C. albicans Als1 and Als3, we performed a quantitative adherence assay by direct microscopic observation using S. cerevisiae strains expressing C. albicans ALS1 and ALS3 with a GFP-tagged C. glabrata strain. Both Als1 and Als3 expressing S. cerevisiae strains showed significantly higher binding (Binding Index = 52.0 ± 3.0 and 58.2 ± 1.4, respectively) compared to S. cerevisiae expressing an empty vector (Binding Index = 19.7 ± 2.3) (Fig 3B).


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 Als3 and Als1 hyphal cell wall adhesins are involved in C. glabrata adherence to C. albicans hyphae.(A) C. glabrata (CgVSY55) adherence to C. albicans Als1, Als3 and Als1/3 deficient strains was measured using fluorescent microscopy. C. glabrata showed a significant (**P<0.001,***P<0.0006) decrease in adherence to C. albicans hyphae of als3Δ/Δ, als1Δ/Δ, and als1/als3Δ/Δ mutants; while C. albicans Als1 and Als3 complementation strains had restored adherence. (B) S. cerevisiae strains expressing C. albicans Als1 and Als3 adhesins and an empty vector (control) were incubated with CgVSY55 and their adherence was quantifed by direct visualization. Both Als1 and Als3 expressing S. cerevisiae strains had a significant (***P<0.001) increase in Binding Index compared to control empty vector. Differences between groups were analyzed by a student’s t test.
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ppat.1005522.g003: C. albicans Als3 and Als1 hyphal cell wall adhesins are involved in C. glabrata adherence to C. albicans hyphae.(A) C. glabrata (CgVSY55) adherence to C. albicans Als1, Als3 and Als1/3 deficient strains was measured using fluorescent microscopy. C. glabrata showed a significant (**P<0.001,***P<0.0006) decrease in adherence to C. albicans hyphae of als3Δ/Δ, als1Δ/Δ, and als1/als3Δ/Δ mutants; while C. albicans Als1 and Als3 complementation strains had restored adherence. (B) S. cerevisiae strains expressing C. albicans Als1 and Als3 adhesins and an empty vector (control) were incubated with CgVSY55 and their adherence was quantifed by direct visualization. Both Als1 and Als3 expressing S. cerevisiae strains had a significant (***P<0.001) increase in Binding Index compared to control empty vector. Differences between groups were analyzed by a student’s t test.
Mentions: We hypothesized that C. glabrata might bind C. albicans cell wall proteins directly. To test candidate C. albicans hyphal wall adhesins required for C. glabrata adhesion, we performed co-adhesion assays with ALS1 and ALS3 deficient C. albicans (Fig 3). We found that C. glabrata had significantly decreased adherence to hyphae of a C. albicans als3Δ/Δ mutant (72.3% reduction), an als1Δ/Δ mutant (28.8% reduction), and an als1/als3Δ/Δ double mutant (86% reduction). ALS1 and ALS3 complementation strains showed restoration of adherence to levels closer to that of wild type strain (Fig 3A). To further validate the role of C. albicans Als1 and Als3, we performed a quantitative adherence assay by direct microscopic observation using S. cerevisiae strains expressing C. albicans ALS1 and ALS3 with a GFP-tagged C. glabrata strain. Both Als1 and Als3 expressing S. cerevisiae strains showed significantly higher binding (Binding Index = 52.0 ± 3.0 and 58.2 ± 1.4, respectively) compared to S. cerevisiae expressing an empty vector (Binding Index = 19.7 ± 2.3) (Fig 3B).

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