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. Author summary: 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 easily neglected before being elevated to species level. Human C. gattii species complex infection was previously confined to the tropical and subtropical regions worldwide. However, in 1999, an outbreak of C. gattii species complex occurred on Vancouver Island in Canada then expanded to the Pacific Northwest in the USA, causing over 200 infections. The highly virulent, highly pathogenic and more resistant to antifungal drugs of this species have become a therapeutic problem. To initiate a better understanding of the infection characteristics and pathogenicity of C. gattii species complex in Guangxi, southern China, the current study aimed to characterize the C. gattii species complex isolates genetically and phenotypically. The ISHAM consensus MLST scheme was utilized to investigate the genetic structure of C. gattii species complex and to correlate their geographic origin, clinical source, virulence factors and antifungal susceptibility. The authors expect that this work can support surveillance and encourage more research and public health initiatives to prevent and control the cryptococcosis cause by C. gattii species complex. [ABSTRACT FROM AUTHOR]