Antifungal Susceptibility Profiles and Resistance Mechanisms of Clinical Diutina catenulata Isolates With High MIC Values.

Xin-Fei Chen,Xue-Fei Du,Wei Zhang,Wen-Hang Yang,Xin Hou,Bin Li,Hong He,Ge Zhang,Wei Kang,Han Zhang,Ying-Xing Li,Xin Fan,Ling-Gui Zou,Dawen Guo ,Jingjing Huang ,Yuhong Pan ,Zhongju Chen ,Jinwen Wang ,Ziyong Sun ,Xiaoyu Liu ,Yingchun Xu

doi:10.3389/fcimb.2021.739496

Abstract

Diutina catenulata (Candida catenulata) is an ascomycete yeast species widely used in environmental and industrial research and capable of causing infections in humans and animals. At present, there are only a few studies on D. catenulata, and further research is required for its more in-depth characterization and analysis. Eleven strains of D. catenulata collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and the CHIF-NET North China Program were identified using matrix-assisted laser desorption ionization–time of flight mass spectrometry and internal transcribed spacer sequencing. The antifungal susceptibility of the Diutina catenulata strains was tested using the Clinical and Laboratory Standards Institute broth microdilution method and Sensititre YeastOne™. Furthermore, ERG11 and FKS1 were sequenced to determine any mutations related to azole and echinocandin resistance in D. catenulata. All isolates exhibited low minimum inhibitory concentration (MIC) values for itraconazole (0.06–0.12 μg/ml), posaconazole (0.06–0.12 μg/ml), amphotericin B (0.25–1 μg/ml), and 5-flucytosine (range, <0.06–0.12 μg/ml), whereas four isolates showed high MICs (≥4 μg/ml) for echinocandins. Strains with high MIC values for azoles showed common ERG11 mutations, namely, F126L/K143R. In addition, L139R mutations may be linked to high MICs of fluconazole. Two amino acid alterations reported to correspond to high MIC values of echinocandin, namely, F621I (F641) and S625L (S645), were found in the hot spot 1 region of FKS1. In addition, one new amino acid alteration, I1348S (I1368), was found outside of the FKS1 hot spot 2 region, and its contribution to echinocandin resistance requires future investigation. Diutina catenulata mainly infects patients with a weak immune system, and the high MIC values for various antifungals exhibited by these isolates may represent a challenge to clinical treatment.

Highlights

In recent years, Candida infections have been on the rise worldwide (Sanguinetti et al, 2015; Pristov and Ghannoum, 2019)
All 11 clinical isolates were identified as D. catenulata by the Autof MS 1000 and Vitek MS
The internal transcribed spacer (ITS) sequences of the study isolates exhibited 100% sequence identity to the corresponding ITS sequences from the reference D. catenulata isolates in GenBank (C. catenulata CBS 565)

Summary

Introduction

Candida infections have been on the rise worldwide (Sanguinetti et al, 2015; Pristov and Ghannoum, 2019). Candida glabrata is the most common cause of candidemia and is resistant to azoles and echinocandins. Candida parapsilosis is another notorious pathogen isolated from patients, which causes outbreaks and multidrug resistance (Arastehfar et al, 2021). These Candida species, though rare, are clinically common and necessitate a better understanding of their pathogenic mechanisms. Diutina catenulata (C. catenulata), an ascomycete, can colonize the digestive tract of animals and humans and cause superficial or deep infections (Crozier, 1977; Radosavljevic et al, 1999; Ha et al, 2018; Cafarchia et al, 2019). The first case of candidemia was diagnosed in a patient with cancer (Radosavljevic et al, 1999)

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