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埃塞俄比亚结核性淋巴结炎患者分离株的耐药性赋予突变及基因多样性

Drug Resistance Conferring Mutation and Genetic Diversity of Isolates in Tuberculosis Lymphadenitis Patients; Ethiopia.

作者信息

Ayalew Sosina, Wegayehu Teklu, Taye Hawult, Wassie Liya, Girma Selfu, Berg Stefan, Mihret Adane

机构信息

Armauer Hansen Research Institute, Addis Ababa, Ethiopia.

Department of Biology, College of Natural Sciences, Arba Minch University (AMU), Arba Minch, Ethiopia.

出版信息

Infect Drug Resist. 2021 Feb 15;14:575-584. doi: 10.2147/IDR.S298683. eCollection 2021.

Abstract

BACKGROUND

Tuberculosis lymphadenitis (TBLN) is a growing public health concern in Ethiopia. However, there is limited information available on gene mutations conferring drug resistance and genetic diversity of isolates from TBLN patients.

METHODS

Drug resistance and genetic diversity analysis were done on 91 from culture positive TBLN patients collected between 2016 and 2017. Detection of mutations conferring resistance was carried out using GenoType MTBDRplus VER 2.0. Thereafter, isolates were typed using spoligotyping.

RESULTS

Out of the 91 strains, mutations conferring resistance to rifampicin (RIF) and isoniazid (INH) were observed in two (2.2%) and six (6.6%) isolates, respectively. The two RIF resistant isolates displayed a mutation at codon 531 in the gene with amino acid change of S531L. Among the six INH resistant strains, four isolates had shown mutation at the gene at codon 315 with amino acid change of S315T, one isolate had a mutation at the gene at codon 15 with amino acid change of C15T and one isolate had a mutation at the gene with unknown amino acid change. All drug resistant isolates were from treatment naive TBLN patients. The dominantly identified Spoligo International Types (SITs) were SIT25, SIT149, and SIT53, respectively; these accounted for 43% of the total number of strains. The isolates were grouped into four main lineages; Lineage 1 (2, 2.2%), Lineage 3 (38, 41.7%), Lineage 4 (49, 53.8%) and Lineage 7 (2, 2.2%). Four out of six (66.7%) isolates with drug resistance conferring mutations belonged to clustered strains (strains with shared SIT).

CONCLUSION

The detection of drug resistant conferring mutation in treatment naïve TBLN patients together with detection of drug resistant isolates among clustered strains might suggest resistant strains' transmission in the community. This needs to be carefully considered to prevent the spread of drug resistant clones in the country.

摘要

背景

结核性淋巴结炎(TBLN)在埃塞俄比亚日益成为公共卫生问题。然而,关于结核性淋巴结炎患者分离株中赋予耐药性的基因突变和遗传多样性的信息有限。

方法

对2016年至2017年间收集的91例培养阳性的结核性淋巴结炎患者进行耐药性和遗传多样性分析。使用GenoType MTBDRplus VER 2.0检测赋予耐药性的突变。此后,使用间隔寡核苷酸分型法对分离株进行分型。

结果

在91株菌株中,分别在2株(2.2%)和6株(6.6%)分离株中观察到赋予利福平(RIF)和异烟肼(INH)耐药性的突变。两株对RIF耐药的分离株在 基因的531密码子处发生突变,氨基酸由S531L改变。在6株对INH耐药的菌株中,4株分离株在 基因的315密码子处发生突变,氨基酸由S315T改变,1株分离株在 基因的15密码子处发生突变,氨基酸由C15T改变,1株分离株在 基因处发生突变,氨基酸改变未知。所有耐药分离株均来自未接受过治疗的结核性淋巴结炎患者。主要鉴定出的间隔寡核苷酸国际类型(SITs)分别为SIT25、SIT149和SIT53;这些占菌株总数的43%。分离株分为四个主要分支;分支1(2株,2.2%)、分支3(38株,41.7%)、分支4(49株,53.8%)和分支7(2株,2.2%)。6株具有赋予耐药性突变的分离株中有4株(66.7%)属于聚集菌株(具有共享SIT的菌株)。

结论

在未接受过治疗的结核性淋巴结炎患者中检测到赋予耐药性的突变,以及在聚集菌株中检测到耐药分离株,可能提示耐药菌株在社区中的传播。为防止耐药克隆在该国传播,这需要仔细考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe2b/7894881/2a1a9a428ca3/IDR-14-575-g0001.jpg

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