AUTHOR=Zhou Ziyi , Zhu Chendi , Ip Margaret , Liu Manjiao , Zhu Zhaoqin , Liu Ryon , Li Xiaomin , Zeng Lingbing , Wu Wenjuan 

TITLE=Molecular Epidemiology and Antifungal Resistance of Cryptococcus neoformans From Human Immunodeficiency Virus-Negative and Human Immunodeficiency Virus-Positive Patients in Eastern China

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.942940

DOI=10.3389/fmicb.2022.942940

ISSN=1664-302X

ABSTRACT=Cryptococcosis is an opportunistic and potentially lethal infection caused by Cryptococcus neoformans and Cryptococcus gattii complex, which affects both immunocompromised and immunocompetent people, and it has become a major public health concern worldwide. In this study, we characterized the molecular epidemiology and antifungal susceptibility of 133 C. neoformans isolates from East China Invasive Fungal Infection Group (ECIFIG), 2017-2020. Isolates were identified to species level by matrix assisted laser desorption ionization-time of flight mass spectrometry and confirmed by IGS1 sequencing. Whole-genome sequencing (WGS) was conducted on three multidrug-resistant isolates. Among the 133 strains, 61 (45.86%) were isolated from HIV and 72 (54.16%) from HIV-uninfected patients. In total, C. neoformans var. grubii accounted for 97.74% (130/133), while C. neoformans var. neoformans was rare (2.06%, 3/133). The strains were further classified into nine STs dominated by ST5 (90.23%, 120/133) with low genetic diversity. No association was observed between STs and HIV status. All strains were wild-type to voriconazole, while high antifungal minimal inhibitory concentrations (MICs) above the epidemiological cutoff values (ECVs) were observed in C. neoformans strains, and more than half of isolates were non-wild-type to amphotericin B (89.15 %,109/133). Eight isolates were resistant to fluconazole, and eight isolates were non-wild -type to 5-fluorocytosine. Furthermore, WGS has verified the novel mutations of FUR1 in 5-fluorocytosine resistant strains. In one isolate, aneuploidy of chromosome 1 with G484S mutation of ERG11 were observed, inducing high-level resistance (MIC: 32 μg/mL) to fluconazole. In general, our data showed that there was no significant difference between HIV and non-HIV patients on STs, and we elucidate the resistant mechanisms of C. neoformans from different perspectives. It is important for clinical therapy and drug usage in the future.