Molecular Diagnostics of Cryptococcus spp. and Immunomics of Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome

Abstract

Cryptococcal infection poses a significant global public health challenge, particularly in regions near the equator. In this review, we offer a succinct exploration of the Cryptococcus spp. genome and various molecular typing methods to assess the burden and genetic diversity of cryptococcal pathogens in the environment and clinical isolates. We delve into a detailed discussion on the molecular pathogenesis and diagnosis of immune reconstitution inflammatory syndrome (IRIS) associated with cryptococcosis, with a specific emphasis on cryptococcal meningitis IRIS (CM-IRIS). Our examination includes the recent literature on CM-IRIS, covering host cellulomics, proteomics, transcriptomics, and genomics.

Keywords: CM-IRIS; HIV; cellulomics; cryptococcal immune reconstitution inflammatory syndrome (C-IRIS); genomics; molecular genetics testing; proteomics; transcriptomics.

Figure 1

UCSC Genome Browser view of basidiomycetes C. neoformans var. neoformans JEC21 (GCF_000091045.1). View Link (accessed 1 February 2024). The following tracks are shown (top to bottom): genome base positions; all gaps; assembly NC_006670.1:761,973-784,475; GC Percent in 5-Base Windows; Perfect Match to Short Sequence; RefSeq gene predictions from NCBI (shown in dark blue); Augustus Gene Predictions (shown in red); CpG islands track; Repeating Elements by RepeatMasker; Simple Tandem Repeats by TRF; and Genomic Intervals Masked by WindowMasker + SDust track.

Figure 2

Top 5 canonical pathways that were overrepresented in upregulated transcript sets in early and late (non-fatal) CM-IRIS subgroups. The top five pathways are those with the largest proportion of transcripts upregulated within the pathway (based on the ingenuity pathway analysis assignment of individual transcripts [82]). Data were extracted for review from [82].