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From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells.

Wächtler B, Wilson D, Haedicke K, Dalle F, Hube B - PLoS ONE (2011)

Bottom Line: We strengthen the concept that hyphal formation is critical for epithelial invasion.Importantly, our data support a model whereby initial epithelial invasion per se does not elicit host damage, but that C. albicans relies on a combination of contact-sensing, directed hyphal extension, active penetration and the expression of novel pathogenicity factors for further inter-epithelial invasion, dissemination and ultimate damage of host cells.Finally, we explore the transcriptional landscape of C. albicans during the early stages of epithelial interaction, and, via genetic analysis, identify ICL1 and PGA34 as novel oral epithelial pathogenicity factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute Jena, Jena, Germany.

ABSTRACT
Candida albicans frequently causes superficial infections by invading and damaging epithelial cells, but may also cause systemic infections by penetrating through epithelial barriers. C. albicans is an unusual pathogen because it can invade epithelial cells via two distinct mechanisms: induced endocytosis, analogous to facultative intracellular enteropathogenic bacteria, and active penetration, similar to plant pathogenic fungi. Here we investigated the molecular basis of C. albicans epithelial interactions. By systematically assessing the contributions of defined fungal pathways and factors to different stages of epithelial interactions, we provide an expansive portrait of the processes and activities involved in epithelial infection. We strengthen the concept that hyphal formation is critical for epithelial invasion. Importantly, our data support a model whereby initial epithelial invasion per se does not elicit host damage, but that C. albicans relies on a combination of contact-sensing, directed hyphal extension, active penetration and the expression of novel pathogenicity factors for further inter-epithelial invasion, dissemination and ultimate damage of host cells. Finally, we explore the transcriptional landscape of C. albicans during the early stages of epithelial interaction, and, via genetic analysis, identify ICL1 and PGA34 as novel oral epithelial pathogenicity factors.

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Adhesion kinetics of C. albicans wild type (WT),                                bud2Δ, rsr1Δ and                                hwp1Δ mutant cells.Oral TR146 epithelial cells were co-incubated with 105                            C. albicans cells for either 20, 60, 120, or 180 min.                            After extensive washing and fixation, the samples were stained and the                            adherent cells were counted under the fluorescence microscope. The                            experiment was performed at least three times in duplicates. The values                            are calculated as percentage of adherent cells compared to wild type                            adherent cells at 180 min (100%). */**, significant                            difference compared to the adhesion of the corresponding WT to oral                            epithelial cells                            (p<0.05/p<0.01).
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pone-0017046-g002: Adhesion kinetics of C. albicans wild type (WT), bud2Δ, rsr1Δ and hwp1Δ mutant cells.Oral TR146 epithelial cells were co-incubated with 105 C. albicans cells for either 20, 60, 120, or 180 min. After extensive washing and fixation, the samples were stained and the adherent cells were counted under the fluorescence microscope. The experiment was performed at least three times in duplicates. The values are calculated as percentage of adherent cells compared to wild type adherent cells at 180 min (100%). */**, significant difference compared to the adhesion of the corresponding WT to oral epithelial cells (p<0.05/p<0.01).

Mentions: The reduced initial adhesion (1 h) but unattenuated invasion (3 h) of group 5 mutants suggested that the respective gene products had major influences on initial adhesion, but that their requirements are then bypassed following extended epithelial contact. We therefore analyzed the adhesion kinetics of wild type C. albicans, as well as mutants lacking the regulatory GTPase Rsr1 (encoded by RSR1), involved in maintenance of cell polarity, directed growth and thigmotropism, its cognate GTPase activating protein (encoded by BUD2) and the adhesin-encoding HWP1. As shown in Fig. 2, adhesion rates at 20 min were low for all tested strains; however, following 1 h incubation, wild type cells began to adhere in greater numbers whilst adhesion rates of bud2Δ, rsr1Δ and hwp1Δ remained low. At 2 h, wild type adhesion had continued to rise and bud2Δ and rsr1Δ strains adhered in greater numbers; however adhesion of hwp1Δ at this time point remained low. Only by 3 h had all strains reached approximately maximum adhesion similar to the wild type (Fig. 2). Therefore, the reduced damage caused by these mutants cannot be explained by fewer initially invading cells. Together these data suggest that primary adhesion of C. albicans to epithelium relies on a combination of factors, including GTPase signaling and the expression of appropriate adhesins, but that following prolonged contact (3 h), defects elicited by the deletion of a single gene are compensated for.


From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells.

Wächtler B, Wilson D, Haedicke K, Dalle F, Hube B - PLoS ONE (2011)

Adhesion kinetics of C. albicans wild type (WT),                                bud2Δ, rsr1Δ and                                hwp1Δ mutant cells.Oral TR146 epithelial cells were co-incubated with 105                            C. albicans cells for either 20, 60, 120, or 180 min.                            After extensive washing and fixation, the samples were stained and the                            adherent cells were counted under the fluorescence microscope. The                            experiment was performed at least three times in duplicates. The values                            are calculated as percentage of adherent cells compared to wild type                            adherent cells at 180 min (100%). */**, significant                            difference compared to the adhesion of the corresponding WT to oral                            epithelial cells                            (p<0.05/p<0.01).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3044159&req=5

pone-0017046-g002: Adhesion kinetics of C. albicans wild type (WT), bud2Δ, rsr1Δ and hwp1Δ mutant cells.Oral TR146 epithelial cells were co-incubated with 105 C. albicans cells for either 20, 60, 120, or 180 min. After extensive washing and fixation, the samples were stained and the adherent cells were counted under the fluorescence microscope. The experiment was performed at least three times in duplicates. The values are calculated as percentage of adherent cells compared to wild type adherent cells at 180 min (100%). */**, significant difference compared to the adhesion of the corresponding WT to oral epithelial cells (p<0.05/p<0.01).
Mentions: The reduced initial adhesion (1 h) but unattenuated invasion (3 h) of group 5 mutants suggested that the respective gene products had major influences on initial adhesion, but that their requirements are then bypassed following extended epithelial contact. We therefore analyzed the adhesion kinetics of wild type C. albicans, as well as mutants lacking the regulatory GTPase Rsr1 (encoded by RSR1), involved in maintenance of cell polarity, directed growth and thigmotropism, its cognate GTPase activating protein (encoded by BUD2) and the adhesin-encoding HWP1. As shown in Fig. 2, adhesion rates at 20 min were low for all tested strains; however, following 1 h incubation, wild type cells began to adhere in greater numbers whilst adhesion rates of bud2Δ, rsr1Δ and hwp1Δ remained low. At 2 h, wild type adhesion had continued to rise and bud2Δ and rsr1Δ strains adhered in greater numbers; however adhesion of hwp1Δ at this time point remained low. Only by 3 h had all strains reached approximately maximum adhesion similar to the wild type (Fig. 2). Therefore, the reduced damage caused by these mutants cannot be explained by fewer initially invading cells. Together these data suggest that primary adhesion of C. albicans to epithelium relies on a combination of factors, including GTPase signaling and the expression of appropriate adhesins, but that following prolonged contact (3 h), defects elicited by the deletion of a single gene are compensated for.

Bottom Line: We strengthen the concept that hyphal formation is critical for epithelial invasion.Importantly, our data support a model whereby initial epithelial invasion per se does not elicit host damage, but that C. albicans relies on a combination of contact-sensing, directed hyphal extension, active penetration and the expression of novel pathogenicity factors for further inter-epithelial invasion, dissemination and ultimate damage of host cells.Finally, we explore the transcriptional landscape of C. albicans during the early stages of epithelial interaction, and, via genetic analysis, identify ICL1 and PGA34 as novel oral epithelial pathogenicity factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute Jena, Jena, Germany.

ABSTRACT
Candida albicans frequently causes superficial infections by invading and damaging epithelial cells, but may also cause systemic infections by penetrating through epithelial barriers. C. albicans is an unusual pathogen because it can invade epithelial cells via two distinct mechanisms: induced endocytosis, analogous to facultative intracellular enteropathogenic bacteria, and active penetration, similar to plant pathogenic fungi. Here we investigated the molecular basis of C. albicans epithelial interactions. By systematically assessing the contributions of defined fungal pathways and factors to different stages of epithelial interactions, we provide an expansive portrait of the processes and activities involved in epithelial infection. We strengthen the concept that hyphal formation is critical for epithelial invasion. Importantly, our data support a model whereby initial epithelial invasion per se does not elicit host damage, but that C. albicans relies on a combination of contact-sensing, directed hyphal extension, active penetration and the expression of novel pathogenicity factors for further inter-epithelial invasion, dissemination and ultimate damage of host cells. Finally, we explore the transcriptional landscape of C. albicans during the early stages of epithelial interaction, and, via genetic analysis, identify ICL1 and PGA34 as novel oral epithelial pathogenicity factors.

Show MeSH
Related in: MedlinePlus