Abstract

The emergence and spread of cryptococcosis caused by the Cryptococcus gattii species complex has become a major public concern worldwide. C. deuterogattii (VGIIa) outbreaks in the Pacific Northwest region demonstrate the expansion of this fungal infection to temperate climate regions. However, infections due to the C. gattii species complex in China have rarely been reported. In this study, we studied eleven clinical strains of the C. gattii species complex isolated from Guangxi, southern China. The genetic identity and variability of these isolates were analyzed via multi-locus sequence typing (MLST), and the phylogenetic relationships among these isolates and global isolates were evaluated. The mating type, physiological features and antifungal susceptibilities of these isolates were also characterized. Among the eleven isolates, six belonged to C. deuterogattii, while five belonged to C. gattii sensu stricto. The C. deuterogattii strains from Guangxi, southern China were genetically variable and clustered with different clinical isolates from Brazil. All strains were MATα, and three C. deuterogattii isolates (GX0104, GX0105 and GX0147) were able to undergo sexual reproduction. Moreover, most strains had capsule and were capable of melanin production when compared to the outbreak strain from Canada. Most isolates were susceptible to antifungal drugs; yet one of eleven immunocompetent patients died of cryptococcal meningitis caused by C. deuterogattii (GX0147). Our study indicated that the highly pathogenic C. deuterogattii may be emerging in southern China, and effective nationwide surveillance of C. gattii species complex infection is necessary.

Highlights

  • Cryptococcus is a life-threatening fungal pathogen of humans and animals[1]

  • Cryptococcosis is a fatal systemic fungal disease caused by Cryptococcus neoformans/gattii species complexes

  • As a former member of the C. neoformans, C. gattii had been neglected before being elevated to species level

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Summary

Introduction

Cryptococcus is a life-threatening fungal pathogen of humans and animals[1]. The infection process of Cryptococcus is usually via the inhalation of airborne spores (or yeast cells) into the respiratory tract and their subsequent dissemination to the central nervous system, causing pulmonary cryptococcosis and cryptococcal meningoencephalitis[1, 2]. During the past two decades, considerable genetic heterogeneity has been demonstrated to occur in the C. neoformans/gattii species complexes by a plethora of molecular methods. Various molecular biological techniques have been used to study the epidemiology and population structure of the Cryptococcus gattii/neoformans species complexes, including random amplification of polymorphic DNA (RAPD) analysis, PCR fingerprinting, amplified fragment length polymorphism (AFLP) analysis, multilocus microsatellite typing (MLMT) analysis and multi-locus sequence typing (MLST) analysis[3]. The identification of the species is commonly based on the MLST protocol standardized by the International Society for Human and Animal Mycology (ISHAM)[5]. The molecular types of C. gattii species complex have been elevated to the species level as C. gattii sensu stricto (AFLP4/VGI), C. deuterogattii (AFLP6/VGII), C. bacillisporus (AFLP5/VGIII), C. tetragattii (AFLP7/VGIV) and C. decagattii (AFLP10/VGIV) [7]. The C. deuterogattii subtype (AFLP6A/VGIIa, AFLP6B/VGIIb and AFLP6C/VGIIc) caused an outbreak in the Pacific Northwest (PNW) region of Canada and the United States[9, 10]

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