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检测导致肝脓肿的溶组织内阿米巴分离株中硝基咪唑抑制浓度的耐药性和筛选穿心莲内酯作为再利用药物。

Creep in nitroimidazole inhibitory concentration among the Entamoeba histolytica isolates causing amoebic liver abscess and screening of andrographolide as a repurposing drug.

机构信息

Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.

Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.

出版信息

Sci Rep. 2023 Jul 27;13(1):12192. doi: 10.1038/s41598-023-39382-1.

DOI:10.1038/s41598-023-39382-1
PMID:37500681
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10374660/
Abstract

Infections by Entamoeba histolytica (E. histolytica) lead to considerable morbidity and mortality worldwide and treatment is reliant on a single class of drugs, nitroimidazoles. Treatment failures and intermittent reports of relapse from different parts of world indicate towards development of clinical drug resistance. In the present study, susceptibility testing of clinical isolates of E. histolytica was carried against metronidazole and tinidazole. Additionally, anti-amoebic property of active compounds of Andrographis paniculata was also evaluated. Prevalence of metronidazole resistance gene (nim) in patients attending hospital was also done to get comprehensive insight of present situation of drug resistance in E. histolytica. Mean inhibitory concentration 50 (IC50) value of E. histolytica isolates against metronidazole and tinidazole was 20.01 and 16.1 µM respectively. Andrographolide showed minimum mean IC50 value (3.06 µM). Significant percentage inhibition of E. histolytica isolates by andrographolide was seen as compared to metronidazole (p = 0.0495). None of E. histolytica isolates showed presence of nim gene. However, in stool samples from hospital attending population, prevalence of nimE gene was found to be 76.6% (69/90) and 62.2% (56/90) in diarrheal and non-diarrheal samples respectively. Inhibitory concentration of commonly used nitroimidazoles against clinical isolates of E. histolytica are on rise. Percentage inhibition of E. histolytica isolates by andrographolide was significantly higher than control drug metronidazole.

摘要

溶组织内阿米巴(E. histolytica)感染在全球范围内导致相当高的发病率和死亡率,治疗依赖于单一类药物,即硝基咪唑类。来自世界各地的治疗失败和间歇性复发报告表明存在临床药物耐药性的发展。在本研究中,对临床分离的溶组织内阿米巴进行了甲硝唑和替硝唑的敏感性测试。此外,还评估了穿心莲有效化合物的抗阿米巴特性。还对就诊于医院的患者中甲硝唑耐药基因(nim)的流行情况进行了检测,以全面了解溶组织内阿米巴的耐药现状。E. histolytica 分离株对甲硝唑和替硝唑的半数抑制浓度(IC50)值分别为 20.01 和 16.1µM。穿心莲内酯的最小平均 IC50 值为 3.06µM。与甲硝唑相比,穿心莲内酯对 E. histolytica 分离株的抑制百分比有显著差异(p=0.0495)。没有 E. histolytica 分离株显示出 nim 基因的存在。然而,在来自医院就诊人群的粪便样本中,nimE 基因的流行率分别为腹泻样本中的 76.6%(69/90)和非腹泻样本中的 62.2%(56/90)。常用硝基咪唑类药物对临床分离的溶组织内阿米巴的抑制浓度正在上升。穿心莲内酯对 E. histolytica 分离株的抑制百分比显著高于对照药物甲硝唑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4eb/10374660/c4d9cd561e1d/41598_2023_39382_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4eb/10374660/af86a79053a6/41598_2023_39382_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4eb/10374660/55bc96078317/41598_2023_39382_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4eb/10374660/4cb96d9ce691/41598_2023_39382_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4eb/10374660/c4d9cd561e1d/41598_2023_39382_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4eb/10374660/af86a79053a6/41598_2023_39382_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4eb/10374660/55bc96078317/41598_2023_39382_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4eb/10374660/4cb96d9ce691/41598_2023_39382_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4eb/10374660/c4d9cd561e1d/41598_2023_39382_Fig4_HTML.jpg

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