Project description:In the last decade, Candida krusei has caused multiple outbreaks of candidemia in Neonatal Intensive Care Units (NICUs) in low-and middle-income countries such as Brazil, India, and South Africa. In India, C. krusei ranks as the sixth cause of candidemia in adult ICUs. Additionally, sporadic outbreaks of nosocomial candidemia in the NICUs are widely reported from India. However, the genetic population of C. krusei causing outbreaks remain largely unknown. In the present study, we used whole genome sequencing to examine the genetic structure of C. krusei population causing candidemia spanning a period of five years (2015-20) in a single NICU in Delhi, India. Further, to evaluate the mechanisms of azole antifungal resistance in C. krusei, we compare the transcriptomic profiles of fluconazole susceptible (FLU-S) and resistant (FLU-R) isolates. Transcriptomic assay was performed in logarithmically growing C. krusei clinical isolates 123/P/19 and 1390/P/18 strains. STAR aligner v.2.5.2b was used to sequence the trimmed reads with the specified reference genome of P. kudriavzevii to determine the unique gene hit counts. A total of 178 genes were differentially expressed by at least 1.5-fold in 1390/P/18 as compared to 123/P/19 isolate. Principal component analysis (PCA) of normalized read counts also depicted almost similar transcriptomic profile between the two C. krusei strains with 53 % variance at principal component 1. Out of 178 differentially expressed genes, 72 were up-regulated and 106 were down-regulated in 1390/P/18 strain compared to 123/P/19 strain. Functionally, genes associated with transport (n=10), mitogen activated protein kinase signaling (MAPK; n=8), transcription factors (TF; n=6) and ergosterol biosynthesis (n=3) were expressed differentially.
2025-09-18 | GSE262836 | GEO
Project description:Whole genome sequencing of Candida dubliniensis clinical bloodstream isolates
| PRJNA1067644 | ENA
Project description:Whole genome sequencing of Candida albicans clinical bloodstream isolates
| PRJNA1068683 | ENA
Project description:Whole genome sequencing of Candida parapsilosis clinical bloodstream isolates
| PRJNA1069103 | ENA
Project description:Whole genome sequencing of Candida glabrata clinical bloodstream isolates
| PRJNA1069094 | ENA
Project description:Whole genome sequencing of Clavispora lusitaniae clinical bloodstream isolates
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.
Project description:Candida glabrata is a human-associated opportunistic fungal pathogen. It shares its niche with Lactobacillus spp. in the gastrointestinal and vaginal tract. In fact, Lactobacillus species are thought to competitively prevent Candida overgrowth. We investigated the molecular aspects of this antifungal effect by analyzing the interaction of C. glabrata strains with Limosilactobacillus fermentum. From a collection of clinical C. glabrata isolates, we identified strains with different sensitivities to L. fermentum in coculture. We analyzed the variation of their expression pattern to isolate the specific response to L. fermentum. C. glabrata-L. fermentum coculture induced genes associated with ergosterol biosynthesis, weak acid stress, and drug/chemical stress. L. fermentum coculture depleted C. glabrata ergosterol. The reduction of ergosterol was dependent on the Lactobacillus species, even in coculture with different Candida species. We found a similar ergosterol-depleting effect with other lactobacillus strains (Lactobacillus crispatus and Lactobacillus rhamosus) on Candida albicans, Candida tropicalis, and Candida krusei. The addition of ergosterol improved C. glabrata growth in the coculture. Blocking ergosterol synthesis with fluconazole increased the susceptibility against L. fermentum, which was again mitigated by the addition of ergosterol. In accordance, a C. glabrata Derg11 mutant, defective in ergosterol biosynthesis, was highly sensitive to L. fermentum. In conclusion, our analysis indicates an unexpected direct function of ergosterol for C. glabrata proliferation in coculture with L. fermentum.
Project description:RNA sequencing was performed on Candida albicans clinical isolates that display normal (isolates: 3560, 3605, 3609, 4108, 4259) or aberrant (isolates: 3534, 3544, 3621, 3636, 4036) beta-glucan masking in response to lactate and hypoxia. Each clinical isolate was grown to exponential phase in GYNB under normoxic conditions and then exposed for 5 h to: (a) 1% lactate; (b) 0% lactate control; (c) hypoxia; or (d) normoxic control. Three independent experiments were performed for each clinical isolate.