부산대학교 도서관

As is the case globally, Cryptococcus gattii is a less frequent cause of cryptococcosis than Cryptococcus neoformans in South Africa. We performed multilocus sequence typing (MLST) and fluconazole susceptibility testing of 146 isolates randomly selected from 750 South African patients with C. gattii disease identified through enhanced laboratory surveillance, 2005 to 2013. The dominant molecular type was VGIV (101/146, 70%), followed by VGI (40/146, 27%), VGII (3/146, 2%) and VGIII (2/146, 1%). Among the 146 C. gattii isolates, 99 different sequence types (STs) were identified, with ST294 (14/146, 10%) and ST155 (10/146, 7%) being most commonly observed. The fluconazole MIC50 and MIC90 values of 105 (of 146) randomly selected C. gattii isolates were 4 μg/ml and 16 μg/ml, respectively. VGIV isolates had a lower MIC50 value compared to non-VGIV isolates, but these values were within one double-dilution of each other. HIV-seropositive patients had a ten-fold increased adjusted odds of a VGIV infection compared to HIV-seronegative patients, though with small numbers (99/136; 73% vs. 2/10; 20%), the confidence interval (CI) was wide (95% CI: 1.93–55.31, p = 0.006). Whole genome phylogeny of 98 isolates of South Africa's most prevalent molecular type, VGIV, identified that this molecular type is highly diverse, with two interesting clusters of ten and six closely related isolates being identified, respectively. One of these clusters consisted only of patients from the Mpumalanga Province in South Africa, suggesting a similar environmental source. This study contributed new insights into the global population structure of this important human pathogen. Author summary: Cryptococcus is the most common cause of meningitis among adults in South Africa. Most human disease is caused by the members of two species complexes within the genus, Cryptococcus neoformans and Cryptococcus gattii. The environmental range of these species complexes, both found in soil, overlaps in southern Africa though C. gattii is a less common human pathogen. C. gattii is divided into six molecular types: VGI, VGII, VGIII, VGIV, VGV and VGVI. In earlier molecular epidemiology studies including relatively few isolates, most southern African isolates were confirmed as molecular type VGIV. We aimed to determine the molecular diversity of C. gattii in South Africa by genotyping patient isolates obtained through laboratory surveillance, 2005–2013. We confirmed that VGIV was the dominant molecular type and that HIV-seropositive patients were more likely to be infected with VGIV compared to those HIV-seronegative. Analysis of the genomes of South African VGIV isolates revealed that they spanned the whole VGIV clade and confirmed that most isolates did not cluster specifically. However, we observed two interesting clusters of closely related isolates, consisting of patients from three neighbouring provinces in South Africa, suggesting a similar environmental source. Further studies of clinical and environmental African C. gattii isolates are needed to gain a better understanding of this pathogen. [ABSTRACT FROM AUTHOR]