Longitudinal genotyping of Candida dubliniensis isolates reveals strain maintenance, microevolution, and the emergence of itraconazole resistance.

Hdl Handle:
http://hdl.handle.net/10147/124500
Title:
Longitudinal genotyping of Candida dubliniensis isolates reveals strain maintenance, microevolution, and the emergence of itraconazole resistance.
Authors:
Fleischhacker, M; Pasligh, J; Moran, G; Ruhnke, M
Affiliation:
Charitè-Universitätsmedizin Berlin Medizinische Klinik m.S. Onkologie u. Hämatologie, Mol. Biol. Labor, Alte Apotheke, CCM, Charitèplatz 1, 10117 Berlin, Germany. michael.fleischhacker@charite.de
Citation:
Longitudinal genotyping of Candida dubliniensis isolates reveals strain maintenance, microevolution, and the emergence of itraconazole resistance. 2010, 48 (5):1643-50 J. Clin. Microbiol.
Journal:
Journal of clinical microbiology
Issue Date:
May-2010
URI:
http://hdl.handle.net/10147/124500
DOI:
10.1128/JCM.01522-09
PubMed ID:
20200288
Abstract:
We investigated the population structure of 208 Candida dubliniensis isolates obtained from 29 patients (25 human immunodeficiency virus [HIV] positive and 4 HIV negative) as part of a longitudinal study. The isolates were identified as C. dubliniensis by arbitrarily primed PCR (AP-PCR) and then genotyped using the Cd25 probe specific for C. dubliniensis. The majority of the isolates (55 of 58) were unique to individual patients, and more than one genotype was recovered from 15 of 29 patients. A total of 21 HIV-positive patients were sampled on more than one occasion (2 to 36 times). Sequential isolates recovered from these patients were all closely related, as demonstrated by hybridization with Cd25 and genotyping by PCR. Six patients were colonized by the same genotype of C. dubliniensis on repeated sampling, while strains exhibiting altered genotypes were recovered from 15 of 21 patients. The majority of these isolates demonstrated minor genetic alterations, i.e., microevolution, while one patient acquired an unrelated strain. The C. dubliniensis strains could not be separated into genetically distinct groups based on patient viral load, CD4 cell count, or oropharyngeal candidosis. However, C. dubliniensis isolates obtained from HIV-positive patients were more closely related than those recovered from HIV-negative patients. Approximately 8% (16 of 194) of isolates exhibited itraconazole resistance. Cross-resistance to fluconazole was only observed in one of these patients. Two patients harboring itraconazole-resistant isolates had not received any previous azole therapy. In conclusion, longitudinal genotyping of C. dubliniensis isolates from HIV-infected patients reveals that isolates from the same patient are generally closely related and may undergo microevolution. In addition, isolates may acquire itraconazole resistance, even in the absence of prior azole therapy.
Item Type:
Article
Language:
en
MeSH:
Adult; Antifungal Agents; Candida; Candidiasis; DNA Fingerprinting; DNA, Fungal; Drug Resistance, Fungal; Evolution, Molecular; Female; Fluconazole; Genotype; HIV Infections; Humans; Itraconazole; Longitudinal Studies; Male; Middle Aged; Mycological Typing Techniques
ISSN:
1098-660X

Full metadata record

DC FieldValue Language
dc.contributor.authorFleischhacker, Men
dc.contributor.authorPasligh, Jen
dc.contributor.authorMoran, Gen
dc.contributor.authorRuhnke, Men
dc.date.accessioned2011-03-14T15:42:40Z-
dc.date.available2011-03-14T15:42:40Z-
dc.date.issued2010-05-
dc.identifier.citationLongitudinal genotyping of Candida dubliniensis isolates reveals strain maintenance, microevolution, and the emergence of itraconazole resistance. 2010, 48 (5):1643-50 J. Clin. Microbiol.en
dc.identifier.issn1098-660X-
dc.identifier.pmid20200288-
dc.identifier.doi10.1128/JCM.01522-09-
dc.identifier.urihttp://hdl.handle.net/10147/124500-
dc.description.abstractWe investigated the population structure of 208 Candida dubliniensis isolates obtained from 29 patients (25 human immunodeficiency virus [HIV] positive and 4 HIV negative) as part of a longitudinal study. The isolates were identified as C. dubliniensis by arbitrarily primed PCR (AP-PCR) and then genotyped using the Cd25 probe specific for C. dubliniensis. The majority of the isolates (55 of 58) were unique to individual patients, and more than one genotype was recovered from 15 of 29 patients. A total of 21 HIV-positive patients were sampled on more than one occasion (2 to 36 times). Sequential isolates recovered from these patients were all closely related, as demonstrated by hybridization with Cd25 and genotyping by PCR. Six patients were colonized by the same genotype of C. dubliniensis on repeated sampling, while strains exhibiting altered genotypes were recovered from 15 of 21 patients. The majority of these isolates demonstrated minor genetic alterations, i.e., microevolution, while one patient acquired an unrelated strain. The C. dubliniensis strains could not be separated into genetically distinct groups based on patient viral load, CD4 cell count, or oropharyngeal candidosis. However, C. dubliniensis isolates obtained from HIV-positive patients were more closely related than those recovered from HIV-negative patients. Approximately 8% (16 of 194) of isolates exhibited itraconazole resistance. Cross-resistance to fluconazole was only observed in one of these patients. Two patients harboring itraconazole-resistant isolates had not received any previous azole therapy. In conclusion, longitudinal genotyping of C. dubliniensis isolates from HIV-infected patients reveals that isolates from the same patient are generally closely related and may undergo microevolution. In addition, isolates may acquire itraconazole resistance, even in the absence of prior azole therapy.-
dc.language.isoenen
dc.subject.meshAdult-
dc.subject.meshAntifungal Agents-
dc.subject.meshCandida-
dc.subject.meshCandidiasis-
dc.subject.meshDNA Fingerprinting-
dc.subject.meshDNA, Fungal-
dc.subject.meshDrug Resistance, Fungal-
dc.subject.meshEvolution, Molecular-
dc.subject.meshFemale-
dc.subject.meshFluconazole-
dc.subject.meshGenotype-
dc.subject.meshHIV Infections-
dc.subject.meshHumans-
dc.subject.meshItraconazole-
dc.subject.meshLongitudinal Studies-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMycological Typing Techniques-
dc.titleLongitudinal genotyping of Candida dubliniensis isolates reveals strain maintenance, microevolution, and the emergence of itraconazole resistance.en
dc.typeArticleen
dc.contributor.departmentCharitè-Universitätsmedizin Berlin Medizinische Klinik m.S. Onkologie u. Hämatologie, Mol. Biol. Labor, Alte Apotheke, CCM, Charitèplatz 1, 10117 Berlin, Germany. michael.fleischhacker@charite.deen
dc.identifier.journalJournal of clinical microbiologyen
dc.description.provinceLeinster-

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