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Mycology

Cryptococcus neoformans Isolates from Transplant Recipients Are Not Selected for Resistance to Calcineurin Inhibitors by Current Immunosuppressive Regimens

Jill R. Blankenship, Nina Singh, Barbara D. Alexander, Joseph Heitman
Jill R. Blankenship
1Departments of Molecular Genetics and Microbiology
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Nina Singh
2Division of Infectious Diseases, Pittsburgh Veterans Affairs Medical Center, Pittsburgh, Pennsylvania
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Barbara D. Alexander
3Medicine
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Joseph Heitman
1Departments of Molecular Genetics and Microbiology
3Medicine
4Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina
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  • For correspondence: heitm001@duke.edu
DOI: 10.1128/JCM.43.1.464-467.2005
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    FIG. 1.

    Drug-hypersensitive and -resistant C. neoformans clinical isolates. (A) Some clinical isolates are hypersensitive to calcineurin inhibitors. Fivefold serial dilutions (starting at ≈10,000 cells) of wild-type strain H99, PAT6ISO1, PAT8ISO1, PAT10ISO1, and PAT22ISO1 were grown on YPD solid medium with no drug (−), 100 μg of CsA per ml, or 1 μg of FK506 per ml for 48 h at 30 or 35°C. (B) Several clinical isolates are resistant to calcineurin inhibitors. Wild-type strain H99, CNA1-1 mutant strain MCC11, and clinical isolates PAT24ISO1, PAT26ISO1, and PAT27ISO1 were diluted as in panel A and grown on YPD solid medium with no drug (−), 100 μg of CsA per ml, or 1 μg of FK506 per ml for 48 h at 30 or 38°C.

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  • TABLE 1.

    Clinical strain data

    StrainaGenotypeOrgan transplantedImmunotherapybSite(s) infectedcSensitivitydRelative capsule sizee
    PAT2ISO1AαLiverMMF, FK506BloodS−
    PAT2ISO2AαLiverMMF, FK506Abdominal abscessS−
    PAT3ISO1AαLungCsACutaneousS+
    PAT4ISO1AαLiverFK506Pulmonary/cutaneousS−
    PAT5ISO1AαLiverFK506CSFS=
    PAT6ISO1AαKidney/pancreasMMF, FK506Lung biopsyHS=
    PAT7ISO1AαLiverMMF, FK506CSFS=
    PAT7ISO2AαLiverMMF, FK506CSFS=
    PAT8ISO1AαLiverLeg biopsyHS+
    PAT9ISO1AαKidneyAbscessS+
    PAT10ISO1AαHeartFK506CSFHS+
    PAT11ISO1AαKidneyFK506CSFS+
    PAT12ISO1BαLiverFK506PulmonaryS=
    PAT13ISO1AαLiverFK506CSFS−
    PAT14ISO1AαKidneyAzathioprineCutaneousS+
    PAT15ISO1AαKidneyAzathioprineCSF/pulmonaryS+
    PAT16ISO1AαKidneyAzathioprineCSFS−
    PAT17ISO1AαKidneyAzathioprineCSFS=
    PAT18ISO1AαKidneyAzathioprineCSFS−
    PAT19ISO1AαHeartMMF, CsACSFS−
    PAT20ISO1AαLiverFK506PulmonaryS=
    PAT21ISO1AαKidneyCsAPulmonary/skin/CSFS−
    PAT22ISO1AαKidneyFK506PulmonaryHS=
    PAT23ISO1AαKidneyFK506PulmonaryS−
    PAT24ISO1AαLiverFK506CSF/pulmonaryR−
    PAT25ISO1AαKidneyAzathioprinePulmonaryS−
    PAT26ISO1AαKidneyAzathioprineCSFR−
    PAT27ISO1AαLiverFK506PulmonaryR=
    PAT28ISO1AαLiverFK506PulmonaryHS=
    PAT29ISO1AαKidney/pancreasFK506CSF/pulmonaryS=
    PAT30ISO1AαKidneyMMF, FK506, predCSF/bloodS+
    PAT30ISO2AαKidneyMMF, FK506, predCSF/bloodS+
    PAT31ISO1AαKidneyMMF, FK506, predCSFS−
    • ↵ a Multiple isolates from the same patient are given the same PAT number with successive ISO numbers (i.e., PAT2ISO1 and PAT2ISO2 are from the same patient).

    • ↵ b Immunosuppressive therapy: data not available for PAT8ISO1 and PAT9ISO1. MMF, mycophenolate mofetil; pred, prednisone.

    • ↵ c CSF, cerebrospinal fluid.

    • ↵ d S, sensitive; HS, hypersensitive; R, resistant.

    • ↵ e Relative capsule size is shown as significantly larger than (+), smaller than (−), or equal to (=) that of H99 (unpaired two-tailed Student t test with 25 samples each).

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Cryptococcus neoformans Isolates from Transplant Recipients Are Not Selected for Resistance to Calcineurin Inhibitors by Current Immunosuppressive Regimens
Jill R. Blankenship, Nina Singh, Barbara D. Alexander, Joseph Heitman
Journal of Clinical Microbiology Jan 2005, 43 (1) 464-467; DOI: 10.1128/JCM.43.1.464-467.2005

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Cryptococcus neoformans Isolates from Transplant Recipients Are Not Selected for Resistance to Calcineurin Inhibitors by Current Immunosuppressive Regimens
Jill R. Blankenship, Nina Singh, Barbara D. Alexander, Joseph Heitman
Journal of Clinical Microbiology Jan 2005, 43 (1) 464-467; DOI: 10.1128/JCM.43.1.464-467.2005
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KEYWORDS

Calcineurin Inhibitors
Cryptococcus neoformans
Cyclosporine
Drug Resistance, Fungal
Immunosuppressive Agents
Organ Transplantation
Tacrolimus

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