Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review

Abstract

The genus Cryptococcus contains two primary species complexes that are significant opportunistic human fungal pathogens: C. neoformans and C. gattii. In humans, cryptococcosis can manifest in many ways, but most often results in either pulmonary or central nervous system disease. Patients with cryptococcosis can display a variety of symptoms on a spectrum of severity because of the interaction between yeast and host. The bulk of our knowledge regarding Cryptococcus and the mechanisms of disease stem from in vitro experiments and in vivo animal models that make a fair attempt, but do not recapitulate the conditions inside the human host. To better understand the dynamics of initiation and progression in cryptococcal disease, it is important to study the genetic and phenotypic differences in the context of human infection to identify the human and fungal risk factors that contribute to pathogenesis and poor clinical outcomes. In this review, we summarize the current understanding of the different clinical presentations and health outcomes that are associated with pathogenicity and virulence of cryptococcal strains with respect to specific genotypes and phenotypes.

Keywords: Cryptococcus; clinical outcomes; clinical presentation; cryptococcal meningitis; genotype; phenotype; pulmonary cryptococcosis; virulence.

Figure 1

Factors that Contribute to Cryptococcosis Infection and Outcome. Abbreviations: Antifungal Therapy (AFT), Treatment (Tx).

Figure 2

The Cryptococcus species complex. Cryptococcal strains are distinguished by species complex, species, serotype, molecular type or lineage, and sequence type. Bold text indicates the Sequence Types that are observed more frequently among clinical isolates (i.e., ST2, ST4-ST9, ST31, ST63, ST93) in certain geographical regions. Genus panel shows the difference in cryptococcal cell shapes that occur in each species complex; C. neoformans strains are often round in shape and C. gattii strains can have an oval to teardrop shaped morphology [2].

Figure 3

Cryptococcal Phenotype Associations with Human Clinical Presentation. Abbreviations: Tuberculosis (TB), Blood Pressure (BP), Headache (HA), Temperature (Temp.), Lumbar Puncture (LP), Cerebral Spinal Fluid (CSF), Intracranial Pressure/Opening Pressure (ICP/OP), Antifungal Therapy (AFT).