Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance.
| dc.contributor.author | Healey, Kelley R | |
| dc.contributor.author | Zhao, Yanan | |
| dc.contributor.author | Perez, Winder B | |
| dc.contributor.author | Lockhart, Shawn R | |
| dc.contributor.author | Sobel, Jack D | |
| dc.contributor.author | Farmakiotis, Dimitrios | |
| dc.contributor.author | Kontoyiannis, Dimitrios P | |
| dc.contributor.author | Sanglard, Dominique | |
| dc.contributor.author | Taj-Aldeen, Saad J | |
| dc.contributor.author | Alexander, Barbara D | |
| dc.contributor.author | Jimenez-Ortigosa, Cristina | |
| dc.contributor.author | Shor, Erika | |
| dc.contributor.author | Perlin, David S | |
| dc.date.accessioned | 2022-10-03T11:09:21Z | |
| dc.date.available | 2022-10-03T11:09:21Z | |
| dc.date.issued | 2016-03 | |
| dc.date.updated | 2022-10-03T11:09:20Z | |
| dc.description.abstract | The fungal pathogen Candida glabrata has emerged as a major health threat since it readily acquires resistance to multiple drug classes, including triazoles and/or echinocandins. Thus far, cellular mechanisms promoting the emergence of resistance to multiple drug classes have not been described in this organism. Here we demonstrate that a mutator phenotype caused by a mismatch repair defect is prevalent in C. glabrata clinical isolates. Strains carrying alterations in mismatch repair gene MSH2 exhibit a higher propensity to breakthrough antifungal treatment in vitro and in mouse models of colonization, and are recovered at a high rate (55% of all C. glabrata recovered) from patients. This genetic mechanism promotes the acquisition of resistance to multiple antifungals, at least partially explaining the elevated rates of triazole and multi-drug resistance associated with C. glabrata. We anticipate that identifying MSH2 defects in infecting strains may influence the management of patients on antifungal drug therapy. | |
| dc.identifier | ncomms11128 | |
| dc.identifier.issn | 2041-1723 | |
| dc.identifier.issn | 2041-1723 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Springer Science and Business Media LLC | |
| dc.relation.ispartof | Nature communications | |
| dc.relation.isversionof | 10.1038/ncomms11128 | |
| dc.subject | Kidney | |
| dc.subject | Animals | |
| dc.subject | Humans | |
| dc.subject | Mice | |
| dc.subject | Candida glabrata | |
| dc.subject | Candidiasis | |
| dc.subject | Disease Models, Animal | |
| dc.subject | Antifungal Agents | |
| dc.subject | Colony Count, Microbial | |
| dc.subject | Drug Resistance, Fungal | |
| dc.subject | Drug Resistance, Multiple | |
| dc.subject | Gene Deletion | |
| dc.subject | Genotype | |
| dc.subject | Phenotype | |
| dc.subject | Mutation | |
| dc.subject | Genes, Fungal | |
| dc.subject | Echinocandins | |
| dc.title | Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Alexander, Barbara D|0000-0001-5868-0529 | |
| pubs.begin-page | 11128 | |
| pubs.issue | 1 | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Medicine | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | Medicine, Infectious Diseases | |
| pubs.publication-status | Published | |
| pubs.volume | 7 |
Files
Original bundle
- Name:
- Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance.pdf
- Size:
- 516.92 KB
- Format:
- Adobe Portable Document Format