Infectomic Analysis of Cryptococcus Infections Using DNA Microarray

Ambrose Jong1, Timothy Triche2, Steven H-M Chen, Sheng-He Huang, Childrens Hospital Los Angeles/University of Southern California;, Childrens Hospital Los Angeles/University of Southern California

The development of high throughput omic approaches, coupled with computational tools, has allowed holistic and integrative studies of infectious diseases (infectomics). Cryptococcus neoformans has a predilection for the central nervous system, resulting in devastating meningoencephalitis. At present, it is unclear how C. neoformans traverses the blood-brain barrier that is formed by the complex tight junctions between brain microvascular endothelial cells (BMEC). Therefore, our laboratories have been keenly interested in infectomic analysis of transcription profiles in human BMEC infected with C. neoformans. We first performed a time-course study of C. neoformans infection of human BMEC, using oligonucleotide microarrays to monitor the infectomes of 12,558 human genes. Co-ordinated regulation of specific mRNAs was found to cluster into functional groups. Notably, we have found dynamic changes in transcription profiles of cytokines that are important for pathogenesis of Cryptococcus meningitis. Our microarray studies have thus far been fruitful in providing new experimental leads and global information for interpreting the pathogenic processes.