| Title: |
Microevolution of Serial Clinical Isolates of Cryptococcus neoformans var. grubii and C. gattii |
| Authors: |
Chen, Y; Farrer, RA; Giamberardino, C; Sakthikumar, S; Jones, A; Yang, T; Tenor, JL; Wagih, O; Van Wyk, M; Govender, NP; Mitchell, TG; Litvintseva, AP; Cuomo, CA; Perfect, JR |
| Source: |
mBio , 8 (2) , Article e00166-17. (2017) |
| Publication Year: |
2017 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Adaptation; Biological; Cerebrospinal Fluid; Cryptococcus gattii; Cryptococcus neoformans; Drug Resistance; Fungal; Evolution; Molecular; Genotype; Humans; Longitudinal Studies; Meningitis; Cryptococcal; Phenotype; Recurrence; South Africa; Temperature; Virulence |
| Description: |
The pathogenic species of Cryptococcus are a major cause of mortality owing to severe infections in immunocompromised as well as immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and in such cases, comparative analyses of the genomes of incident and relapse isolates may reveal evidence of determinative, microevolutionary changes within the host. Here, we analyzed serial isolates cultured from cerebrospinal fluid specimens of 18 South African patients with recurrent cryptococcal meningitis. The time between collection of the incident isolates and collection of the relapse isolates ranged from 124 days to 290 days, and the analyses revealed that, during this period within the patients, the isolates underwent several genetic and phenotypic changes. Considering the vast genetic diversity of cryptococcal isolates in sub-Saharan Africa, it was not surprising to find that the relapse isolates had acquired different genetic and correlative phenotypic changes. They exhibited various mechanisms for enhancing virulence, such as growth at 39°C, adaptation to stress, and capsule production; a remarkable amplification of ERG11 at the native and unlinked locus may provide stable resistance to fluconazole. Our data provide a deeper understanding of the microevolution of Cryptococcus species under pressure from antifungal chemotherapy and host immune responses. This investigation clearly suggests a promising strategy to identify novel targets for improved diagnosis, therapy, and prognosis.IMPORTANCE Opportunistic infections caused by species of the pathogenic yeast Cryptococcus lead to chronic meningoencephalitis and continue to ravage thousands of patients with HIV/AIDS. Despite receiving antifungal treatment, over 10% of patients develop recurrent disease. In this study, we collected isolates of Cryptococcus from cerebrospinal fluid specimens of 18 patients at the time of their diagnosis and when they relapsed several months later. We then sequenced and ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10038123/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10038123/1/mBio-2017-Chen-.pdf; https://discovery.ucl.ac.uk/id/eprint/10038123/ |
| Rights: |
open |
| Accession Number: |
edsbas.7634BC9B |
| Database: |
BASE |