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人β-防御素-3 对白色念珠菌的抑制作用。

The Inhibitory Effect of Human Beta-defensin-3 on Isolated from Patients with Candidiasis.

机构信息

Translational Research in Inflammation and Immunology Research Unit, Faculty of Medicine, Chulalongkorn University , Bangkok, Thailand.

Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand.

出版信息

Immunol Invest. 2021 Jan;50(1):80-91. doi: 10.1080/08820139.2020.1755307. Epub 2020 Apr 22.

Abstract

is a common non- species found in patients with candidiasis and it sometimes develops antifungal resistance. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide of immune system active against various types of microbes including . This study investigated antifungal activity of hBD-3 and its synergistic effect with a first-line antifungal agent on clinical isolates. . were characterised in patients with candidiasis. The antifungal activities of hBD-3 and fluconazole against were evaluated using Broth microdilution assay. The synergistic activity of these two agents was determined by checkerboard microdilution and time-killing assays. The cytotoxicity of hBD-3 was evaluated using LDH-cytotoxicity colorimetric assay. Of 307 episodes from 254 patients diagnosed with candidiasis, was found in 21 clinical isolates. Antifungal susceptibility tests of were performed, fluconazole demonstrated an inhibitory effect at concentrations of 0.25-8 μg/ml, but one antifungal resistant strain was identified (>64 μg/ml). hBD-3 showed an inhibitory effect against all selected strains at concentrations of 50-75 μg/ml and exhibited a synergistic effect with fluconazole at the fractional inhibitory concentration index (FICI) of 0.25-0.50. A concentration of 25 μg/ml of hBD-3 alone showed no cytotoxicity but synergistic activity was seen with fluconazole. In conclusion, hBD-3 has antifungal activity against and synergistic effects with fluconazole at concentrations that alone, have no cytotoxicity. hBD-3 could be used as an adjunctive therapy with first-line antifungal agents for patients with infection particularly those infected with fluconazole-resistant strains.

摘要

是一种常见的非物种,存在于念珠菌病患者中,它有时会产生抗真菌耐药性。人β-防御素-3(hBD-3)是一种免疫系统的抗菌肽,对包括在内的各种类型的微生物具有活性。本研究调查了 hBD-3 的抗真菌活性及其与一线抗真菌药物对临床分离株的协同作用。从 254 例确诊为念珠菌病的患者中,共采集了 307 例发作,从 21 例临床分离株中发现了。对进行了抗真菌药敏试验,氟康唑在 0.25-8μg/ml 浓度下表现出抑制作用,但鉴定出一株抗真菌耐药株(>64μg/ml)。hBD-3 在 50-75μg/ml 浓度下对所有选定的菌株均表现出抑制作用,并在分数抑制浓度指数(FICI)为 0.25-0.50 时与氟康唑表现出协同作用。25μg/ml 的 hBD-3 单独使用时没有细胞毒性,但与氟康唑联合使用时表现出协同作用。总之,hBD-3 对具有抗真菌活性,与氟康唑在浓度上具有协同作用,而单独使用时无细胞毒性。hBD-3 可与一线抗真菌药物联合用于治疗感染,特别是感染氟康唑耐药株的患者。

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