Abstract
The human pathogenic Cryptococcus species are the main agents of fungal meningitis in humans and the causes of other diseases collectively called cryptococcosis. There are at least eight evolutionary divergent lineages among these agents, with different lineages showing different geographic and/or ecological distributions. In this review, we describe the main strain typing methods that have been used to analyze the human pathogenic Cryptococcus and discuss how molecular markers derived from the various strain typing methods have impacted our understanding of not only cryptococcal epidemiology but also its evolutionary histories. These methods include serotyping, multilocus enzyme electrophoresis, electrophoretic karyotyping, random amplified polymorphic DNA, restriction fragment length polymorphism, PCR-fingerprinting, amplified fragment length polymorphism, multilocus microsatellite typing, single locus and multilocus sequence typing, matrix-assisted laser desorption/ionization time of flight mass spectrometry, and whole genome sequencing. The major findings and the advantages and disadvantages of each method are discussed. Together, while controversies remain, these strain typing methods have helped reveal (i) the broad phylogenetic pattern among these agents, (ii) the centers of origins for several lineages and their dispersal patterns, (iii) the distributions of genetic variation among geographic regions and ecological niches, (iv) recent hybridization among several lineages, and (v) specific mutations during infections within individual patients. However, significant challenges remain. Multilocus sequence typing and whole genome sequencing are emerging as the gold standards for continued strain typing and epidemiological investigations of cryptococcosis.
Highlights
The human pathogenic Cryptococcus species are among the biggest causes of mobility and mortality in humans
Perfect et al noted that pulsed-field gel electrophoresis (PFGE) karyotyping could be used to exclude the possibility of nosocomial spread of Cryptococcus neoformans species complex (CNSC) in one clinical situation and supported relapse in two other cases due to its variable chromosome sizes between isolates (Perfect et al, 1993). These results indicated the PFGE karyotyping can be a powerful method for discriminating strains and for epidemiological studies of CNSC and Cryptococcus gattii species complex (CGSC)
Over the past 30 years, we have seen a rapid development of strain typing methods to differentiate species and strains of this group of important human fungal pathogens (Figure 1)
Summary
The human pathogenic Cryptococcus species are among the biggest causes of mobility and mortality in humans. Since the 1980s, several molecular typing methods have been developed to study the epidemiology and genetic diversity of these two species complexes (Table 1). These methods primarily assay DNA sequence variations among strains and lineages and include random amplified polymorphic DNA (RAPD), PCRfingerprinting, amplified fragment length polymorphisms (AFLP), PCR-restriction fragment length polymorphisms (PCR-RFLP), single locus sequence typing (SLST), multilocus sequence typing (MLST), multilocus microsatellite typing (MLMT), and whole genome sequencing (Sidrim et al, 2010; Li et al, 2013; Cuomo et al, 2018). Together, these methods have allowed the identifications of individual and/or groups of strains, clarified the phylogenetic diversity within and between the two species complexes, revealed both recent and ancient hybridizations among lineages, and identified both broad geographic patterns of strain genotype distributions and local transmissions and microevolutions. We discuss how the methods have enabled other types of studies on the origins, virulence, and drug resistance in this important group of fungal pathogens
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
