Antifungal susceptibility and molecular characteristics of Cryptococcus spp. based on whole-genome sequencing in Zhejiang Province, China

Abstract

Cryptococcus spp. is a complex species that often causes cryptococcosis, which is one of the most common opportunistic infections in adults living with HIV and has very high morbidity and mortality rates. This study aimed to investigate the antifungal susceptibility profiles and epidemiological characteristics of the Cryptococcus neoformans species complex (CNSC) and the Cryptococcus gattii species complex (CGSC) in Zhejiang Province, China. A total of 177 CNSC and 3 CGSC isolates were collected, and antifungal susceptibility was tested by FUNGUS 3 and verified with an E-test. Moreover, multiple classification methods and genomic analyses were performed. The majority of the isolates (96.11%) were C. neoformans (formerly C. neoformans var. grubii) (ST5-VNI-A-α). Our study highlights that most of the patients with cryptococcosis were non-HIV patients in China, and nearly half of them did not have underlying diseases that led to immune insufficiency. Most of the Cryptococcus spp. isolates in this study were sensitive to common antifungal drugs. Two 5-flucytosine (5-FC)-resistant strains were identified, and FUR1 mutation was detected in the 5-FC-resistant isolates. Typing based on whole-genome sequencing (WGS) showed better discrimination than that achieved with multilocus sequence typing (MLST) and indicated a clear population structure. A phylogenetic analysis based on WGS included more genomic information than traditional classification methods.

In vitro characterization and molecular epidemiology of Cryptococcus spp. isolates from non-HIV patients in Guangdong, China

“…Similarly, strains with 5-fluorocytosine and fluconazole MIC >16 μg/mL have also been reported in other Asian countries, such as Thailand, India and Indonesia ( Khayhan et al, 2013 ). To date, the rate of resistance to amphotericin B ranges from 1 to 75% ( Li et al, 2020 ; Zhang et al, 2022 ; Zhou et al, 2022 ). While there is no apparent upward trend in the annual increase of antifungal resistance among Cryptococcus strains in the Guangdong region, a substantial proportion of isolates do exhibit MIC values near the clinical breakpoints, particularly against amphotericin B.…”

“…Therefore, a comprehensive analysis in the context of clinical use and prognosis in the region should be carefully performed. In addition, studies have also found that the emergence of drug-resistant strains could be associated with gene mutations ( Li et al, 2020 ; Zhang et al, 2022 ; Zhou et al, 2022 ). Notably, although itraconazole, voriconazole and posaconazole are not recommended as the first choice by the guidelines for the treatment of cryptococcosis, clinical strains in the region maintain a low MIC ( Table 2 ), which was consistent with the findings from other studies ( Khayhan et al, 2013 ; Fan et al, 2016 ) that indicated that itraconazole, voriconazole and posaconazole can be used as alternatives when the strains isolated from patients became resistant to first-line agents.…”

“…Molecular epidemiological studies on Cryptococcus have previously been carried out in some areas of China ( Liang et al, 2014 ; Dou et al, 2015 , 2017 ; Chen Y. H. et al, 2018 ; Xiao et al, 2018 ; Zhang et al, 2022 ; Zhou et al, 2022 ). These studies showed that the C. neoformans Grubii variant and VNI type were dominant in China.…”

A potent endophytic fungus Purpureocillium lilacinumYZ1 protects against Fusarium infection in field‐grown wheat

“…Similarly, positive outcomes have been reported with fungal biocontrol agents (BCAs) such as Cryptococcus spp. (Zhang et al ., 2022), Trichoderma (Mondani et al ., 2021), Simplicillium (Abaya et al ., 2021), Clonostachys spp. (Abdellatif et al ., 2022), and various other species (Comby et al ., 2017; Rojas et al ., 2020; Hao et al ., 2021; Noel et al ., 2022).…”