Project description:Candida tropicalis is an opportunistic pathogen which causes candidiasis in immune-compromised individuals. It is one of the members of the non-albicans group of Candida that are known to be azole resistant and is frequently seen in individuals being treated for cancers, HIV-infection and bone-marrow transplant. Although the genome of C. tropicalis was sequenced in the year 2009, the genome annotation has not been supported by experimental validation. In the present study, we have carried out in-depth proteomic profiling of C. tropicalis using high-resolution Fourier transform mass spectrometry and mapped ~44% of the computationally predicted protein-coding genes with peptide level evidence. In addition to identifying 2,740 proteins in the cell lysate of this yeast, we also analysed the proteome of the conditioned media of C. tropicalis culture and identified several unique secreted proteins among a total of 780 proteins. By subjecting the mass spectrometry data derived from cell lysate and conditioned media to proteogenomic analysis, we identified 86 novel genes, 12 novel exons and corrected 49 computationally predicted gene models. To our knowledge, this is the first high-throughput proteomic study to refine the genome annotation of C. tropicalis.
Project description:Candida species are components of the normal intestinal microbiota and are under constant exposure to bacterial metabolites, including secondary bile salts. Here, we examined the effect of a secondary bile salt, sodium deoxycholate (NaDCA), on the formation of biofilms by Candida tropicalis. In contrast to C. albicans, C. tropicalis tended to maintain its absolute biofilm biomass and surface hydrophobicity in the presence of NaDCA. Fluorescent 3D microscopic imaging of the biofilm revealed that NaDCA treatment reduced filamentous projection to the top of the biofilm. RNA-seq analysis revealed that some genes, especially those associated with iron metabolism, were differentially expressed in NaDCA-treated C. tropicalis. Although NaDCA altered the appearance of C. tropicalis biofilms, analysis of the expression of key virulence factor genes encoding agglutinin-like sequences and candidalysin revealed that these genes were less affected by NaDCA in C. tropicalis than in C. albicans. High-iron exposure had a negative effect on C. tropicalis biofilm biomass. These results suggest a difference in the intestinal niche occupied by C. albicans and C. tropicalis according to the local availability of secondary bile salts.
Project description:Phenotypic switching is a strategy by which microbial organisms adapt to environmental changes. The human fungal pathogens, Candida albicans and Candida tropicalis, are closely related species and capable of undergoing morphological transitions. C. albicans primarily exists in human or warm-blooded animals as a commensal, whereas C. tropicalis not only exists as a commensal but also is widely distributed in the environment. In this study, To elucidate the regulatory mechanism of environmental pH on white-opaque switching in C. tropicalis, we performed RNA-Seq analysis under three pH conditions (pH 5.0, pH 7.0, and pH 8.0).
Project description:Candida tropicalis is a leading cause of invasive candidiasis in the Asia-Pacific region, with mortality rates exceeding 50%. The rising prevalence of azole resistant clinical strains, particularly in this region, presents a significant clinical challenge. In this study, we analyzed 1,032 C. tropicalis isolates, including 1,016 clinical isolates collected over nine years from 27 hospitals across India, as well as 16 environmental isolates. Fluconazole resistance was detected in 5.1% of clinical isolates, with more than half also exhibiting cross-resistance to voriconazole and itraconazole. Multilocus sequence typing (MLST) and phylogenomic analysis of 1,571 global isolates, confirmed the clonal emergence and persistence of azole- resistant MLST clade 4 strains in Indian hospitals. Genomic analysis revealed that Indian isolates cluster closely with azole resistant strains from China, Singapore, and Taiwan. Azole resistance was found to be multifactorial, involving well-characterized hotspot mutations in the ERG11 gene (Y132F, S154F), ERG11 gene amplification (2–7.5 copies), and significant overexpression of ERG11. Transcriptomic profiling showed significant up regulation of virulence-associated genes in the fluconazole-resistant isolate. Notably, ALS7, a member of the agglutinin-like sequence (ALS) family involved in cell adhesion along with Secreted Aspartyl Proteinases (SAP) genes SAP7 and SAP9, were significantly upregulated in fluconazole-resistant isolates. Additionally, fluconazole-resistant isolates exhibited significantly enhanced biofilm formation compared to fluconazole-susceptible strains, indicating a higher virulence potential. Furthermore, fluconazole-resistant isolates exhibited reduced β-glucan exposure, a trait linked to immune evasion, and showed greater survival in both neutrophil and macrophage killing assays. Together, our findings provide comprehensive genomic and phenotypic evidence supporting the emergence, persistence, and increased pathogenic potential of azole-resistant C. tropicalis clade 4 in Indian hospitals. A deeper understanding of the epidemiological trends and molecular mechanisms driving drug resistance in C. tropicalis is essential for improving diagnostic accuracy, optimising antifungal susceptibility testing, and informing effective clinical management strategies.
Project description:Phenotypic plasticity, the ability to switch between different morphological types, plays critical roles in environmental adaptation, leading to infections, and allowing for sexual reproduction in pathogenic Candida species. Candida tropicalis, which is both an emerging human fungal pathogen and an environmental fungus, can switch between two heritable cell types termed white and opaque. In this study, we report the discovery of a novel phenotype in C. tropicalis, named the gray phenotype. Similar to Candida albicans and Candida dubliniensis, white, gray, and opaque cell types of C. tropicalis also form a tristable switching system, where gray cells are relatively small and elongated. In C. tropicalis, gray cells exhibit intermediate levels of mating competency and virulence in a mouse systemic infection model compared to the white and opaque cell types, express a set of cell type-enriched genes, and exhibit both common and species-specific biological features. The key regulators of white-opaque transitions, Wor1 and Efg1, are not required for the gray phenotype. A comparative study of the gray phenotypes in C. tropicalis, C. albicans, and C. dubliniensis provides clues to explain the species differences in terms of virulence, ecological niches, and prevalence among these three species.
Project description:Homo sapiens fresh whole blood was infected with Candida tropicalis. RNA-pool of both species extracted at 0min (control), 15, 30, 60, 120, 240 min. Samples are rRNA depleted. Measurement of Candida tropicalis gene expression.
Project description:Purpose: We compared the expression profile of three fluconazole resistant clinical isolates to two fluconazole sensitive clinical isolates, from the same patient, all containing mutation in the trancription factor Mrr1, to define the Mrr1 regulon in Candida lusitaniae.
2018-11-14 | GSE111421 | GEO
Project description:Whole genome resequencing of clinical isolates of Candida tropicalis
Project description:Comparative analysis of genome wide binding profile of Ncb2 in azole sensitive (AS, Gu4) and azole resistant (AR, Gu5) clinical isolates of Candida albicans. The goal was to study the role of Ncb2 in acquisition of drug resistance by comparing the binding profiles of Ncb2 in both the isolates.