Candida albicans cell-type switching and functional plasticity in the mammalian host

Abstract

Candida albicans is a ubiquitous commensal of the mammalian microbiome as well as the most prevalent fungal pathogen of humans. A cell type transition between C. albicans yeast and hyphal morphologies was thought to underlie much of the variation in virulence in different host tissues. However, novel yeast-like cell morphotypes, including opaquea/α, gray, and GUT cell types, were recently reported that exhibit pronounced differences in vitro and in animal models of commensalism and disease. In this Review, we explore the characteristics of the classic cell types yeast, hyphae, pseudohyphae and chlamydospores as well as the newly identified yeast-like morphotypes. We highlight emerging knowledge about the associations of these different morphotypes with different host niches, virulence potential as well as the environmental cues and signalling pathways involved in the morphological transitions.

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

“…The algorithm was based on the levels of phosphorylated peptides containing amino acid sequence motifs characteristic of the substrate specificity of known protein kinases ( Fig 4C ). Strikingly, in contrast to the current models [ 2 , 3 , 5 ], this analysis revealed PKA activity was not significantly different before and after hyphal induction in the WT or PR13 strains ( Fig 4D ). Furthermore, control studies showed that the levels of the PKA subunits Bcy1 and Tpk2 remained constant during hyphal induction ( S2 Fig ).…”

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

“…The algorithm was based on the levels of phosphorylated peptides containing amino acid sequence motifs characteristic of the substrate specificity of known protein kinases ( Fig 4C ). Strikingly, in contrast to the current models [ 2 , 3 , 5 ], this analysis revealed PKA activity was not significantly different before and after hyphal induction in the WT or PR13 strains ( Fig 4D ). Furthermore, control studies showed that the levels of the PKA subunits Bcy1 and Tpk2 remained constant during hyphal induction ( S2 Fig ).…”

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

“…4c). Strikingly, in contrast to the current models 2, 3, 5 , this analysis revealed PKA activity was not significantly different before and after hyphal induction in the WT or PR13 strains (Fig. 4d).…”

“…The algorithm was based on the levels of phosphorylated peptides containing amino acid sequence motifs characteristic of the substrate specificity of known protein kinases (Fig 4C). Strikingly, in contrast to the current models [2,3,5], this analysis revealed PKA activity was not significantly different before and after hyphal induction in the WT or PR13 strains (Fig 4D ). However, the PR13 hgc1Δ/Δ mutant produced a lower level of filamentous cells (36%) compared to the PR13 strain (61%).…”

Potent In Vitro Activity of Citrus aurantium Essential Oil and Vitis vinifera Hydrolate Against Gut Yeast Isolates from Irritable Bowel Syndrome Patients—The Right Mix for Potential Therapeutic Use

“…As reported in a recent review, the morphological plasticity of Candida albicans cells makes this fungus able to adapt to the different niches present in the gut of the host organisms. Generally, the production of C. albicans hyphae and pseudo-hyphae is typical of cellular models of virulence specialized in the commensalism [38]. The above are in agreement with what has been observed on C. albicans clinical isolates of IBS patients [33] where the gut microbiota is characterized by a greater abundance of C. albicans cells, more virulent than in healthy subjects.…”

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

“…The algorithm was based on the levels of phosphorylated peptides containing amino acid sequence motifs characteristic of the substrate specificity of known protein kinases ( Fig 4C ). Strikingly, in contrast to the current models [ 2 , 3 , 5 ], this analysis revealed PKA activity was not significantly different before and after hyphal induction in the WT or PR13 strains ( Fig 4D ). Furthermore, control studies showed that the levels of the PKA subunits Bcy1 and Tpk2 remained constant during hyphal induction ( S2 Fig ).…”

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

“…4c). Strikingly, in contrast to the current models 2, 3, 5 , this analysis revealed PKA activity was not significantly different before and after hyphal induction in the WT or PR13 strains (Fig. 4d).…”

“…The algorithm was based on the levels of phosphorylated peptides containing amino acid sequence motifs characteristic of the substrate specificity of known protein kinases (Fig 4C). Strikingly, in contrast to the current models [2,3,5], this analysis revealed PKA activity was not significantly different before and after hyphal induction in the WT or PR13 strains (Fig 4D ). However, the PR13 hgc1Δ/Δ mutant produced a lower level of filamentous cells (36%) compared to the PR13 strain (61%).…”

Potent In Vitro Activity of Citrus aurantium Essential Oil and Vitis vinifera Hydrolate Against Gut Yeast Isolates from Irritable Bowel Syndrome Patients—The Right Mix for Potential Therapeutic Use

“…As reported in a recent review, the morphological plasticity of Candida albicans cells makes this fungus able to adapt to the different niches present in the gut of the host organisms. Generally, the production of C. albicans hyphae and pseudo-hyphae is typical of cellular models of virulence specialized in the commensalism [38]. The above are in agreement with what has been observed on C. albicans clinical isolates of IBS patients [33] where the gut microbiota is characterized by a greater abundance of C. albicans cells, more virulent than in healthy subjects.…”

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

“…The algorithm was based on the levels of phosphorylated peptides containing amino acid sequence motifs characteristic of the substrate specificity of known protein kinases ( Fig 4C ). Strikingly, in contrast to the current models [ 2 , 3 , 5 ], this analysis revealed PKA activity was not significantly different before and after hyphal induction in the WT or PR13 strains ( Fig 4D ). Furthermore, control studies showed that the levels of the PKA subunits Bcy1 and Tpk2 remained constant during hyphal induction ( S2 Fig ).…”

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

“…4c). Strikingly, in contrast to the current models 2, 3, 5 , this analysis revealed PKA activity was not significantly different before and after hyphal induction in the WT or PR13 strains (Fig. 4d).…”

“…The algorithm was based on the levels of phosphorylated peptides containing amino acid sequence motifs characteristic of the substrate specificity of known protein kinases (Fig 4C). Strikingly, in contrast to the current models [2,3,5], this analysis revealed PKA activity was not significantly different before and after hyphal induction in the WT or PR13 strains (Fig 4D ). However, the PR13 hgc1Δ/Δ mutant produced a lower level of filamentous cells (36%) compared to the PR13 strain (61%).…”

Potent In Vitro Activity of Citrus aurantium Essential Oil and Vitis vinifera Hydrolate Against Gut Yeast Isolates from Irritable Bowel Syndrome Patients—The Right Mix for Potential Therapeutic Use

“…As reported in a recent review, the morphological plasticity of Candida albicans cells makes this fungus able to adapt to the different niches present in the gut of the host organisms. Generally, the production of C. albicans hyphae and pseudo-hyphae is typical of cellular models of virulence specialized in the commensalism [38]. The above are in agreement with what has been observed on C. albicans clinical isolates of IBS patients [33] where the gut microbiota is characterized by a greater abundance of C. albicans cells, more virulent than in healthy subjects.…”