Comparison of Cryptococcus RNA Expression in Meningitis and Pneumonia in Organ Transplant Recipients

We sought to determine identification of proteins that are upregulated in cryptococcal isolates associated with Central Nervous System (CNS) infection and death more than in other isolates. Isolates included in the study were obtained from cultures of blood or tissue from solid organ transplant recipients on immunosuppression at the time of infection. Isolates were collected over time and frozen in -80°C until DNA and RNA extraction. Isolates came from 18 patients, 9 with pneumonia who survived and 9 with meningitis who died. Once the isolates were cultured from deep freeze and DNA and RNA were extracted, microarray analysis was performed to assess differences in isolates of meningitis compared with isolates from pneumonia. All of the isolates were determined to be similar strains of Cryptococcus, Cryptococcus neoformans variant grubii, indicating no significant genetic differences that should account for the expression differences. Microarray analysis revealed numerous genes that were differentially expressed. Many of these genes appeared to be located in the subtelomeric region of the chromosomes, indicating these may be regulators affecting several genes downstream. Genes were also identified utilizing the Broad Institute Cryptococcal database. Some genes found to be overexpressed in the M group included those involved with hydrolase activity, tRNA binding, metal ion binding, sugar transporter genes, and sphingolipid synthesis. The results of this study will be validated in animal models and larger clinical translational studies. The data will also provide further data for the Broad Institute cryptococcal data base as well.