Geographically Structured Populations of Cryptococcus neoformans Variety grubii in Asia Correlate with HIV Status and Show a Clonal Population Structure

Abstract

Cryptococcosis is an important fungal disease in Asia with an estimated 140,000 new infections annually the majority of which occurs in patients suffering from HIV/AIDS. Cryptococcus neoformans variety grubii (serotype A) is the major causative agent of this disease. In the present study, multilocus sequence typing (MLST) using the ISHAM MLST consensus scheme for the C. neoformans/C. gattii species complex was used to analyse nucleotide polymorphisms among 476 isolates of this pathogen obtained from 8 Asian countries. Population genetic analysis showed that the Asian C. neoformans var. grubii population shows limited genetic diversity and demonstrates a largely clonal mode of reproduction when compared with the global MLST dataset. HIV-status, sequence types and geography were found to be confounded. However, a correlation between sequence types and isolates from HIV-negative patients was observed among the Asian isolates. Observations of high gene flow between the Middle Eastern and the Southeastern Asian populations suggest that immigrant workers in the Middle East were originally infected in Southeastern Asia.

Antifungal Drug Susceptibility and Phylogenetic Diversity among Cryptococcus Isolates from Dogs and Cats in North America

“…The most prevalent C. neoformans sequence type, ST23, is a prevalent type found previously in the United States, Asia, Africa, and Europe in both environmental and clinical specimens (40)(41)(42)(43). Other sequence types identified in our study have been also reported before from Asia (ST5 and ST32), Africa (ST5, ST23, ST39, and ST43), and the United States (ST32) (40)(41)(42)(43)(44)(45).…”

“…The most prevalent C. neoformans sequence type, ST23, is a prevalent type found previously in the United States, Asia, Africa, and Europe in both environmental and clinical specimens (40)(41)(42)(43). Other sequence types identified in our study have been also reported before from Asia (ST5 and ST32), Africa (ST5, ST23, ST39, and ST43), and the United States (ST32) (40)(41)(42)(43)(44)(45). Molecular type VNI, VNII, VGI, and VGII isolates from dogs and cats in this study had sequence types that were identical or closely related to those of the reference VGI and VGII strains, respectively, supporting the more clonal relationship of these populations as described previously (15,16).…”

Molecular epidemiology of Cryptococcus neoformans and Cryptococcus gattii in China between 2007 and 2013 using multilocus sequence typing and the DiversiLab system

“…A total of 76 VNI (91.6 %) were identified as MLST ST5, followed by one each of ST31, ST63, and ST296 for VNI, one ST295 for VNB, one ST332 for VGI, and one ST182 for VGII. Some studies have shown that ST5 was the most frequent ST in China and other Asian countries [19,36]. A total of 476 isolates of C. neoformans var.…”

Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

“…Another one has been recorded from 1983 to 2009 in North and South America, in Europe and in Asia (Khayhan et al, 2013). C. gattii and C. neoformans also exhibit very typical near-clades (Tibayrenc and Ayala, 2014b), corroborated by various molecular markers, including AFLP, MLST, PCR fingerprinting, RAPD and RFLP, and strongly linked to serotypes (Bovers et al, 2008;Campbell et al, 2005;Campbell and Carter, 2006;Carriconde et al, 2011;Chaturvedi and Chaturvedi, 2011;Fraser et al, 2005;Khayhan et al, 2013;Lin and Heitman, 2006;Litvintseva and Mitchell, 2012;Ngamskulrungroj et al, 2009;Voelz et al, 2013;Xu, 2006a). In C. gattii, there are 4 'molecular types' (near-clades) I to IV.…”

“…a,b Didelot and Falush (2007) b Downing et al (2011) c Khayhan et al (2013) b,e Didelot (2010) b Duffy et al (2013) c,e Lin and Heitman (2006) b Dos Vultos et al…”