Mycobacterium tuberculosis Sub-Lineage 4.2.2/SIT149 as Dominant Drug-Resistant Clade in Northwest Ethiopia 2020-2022: In-silico Whole-Genome Sequence Analysis

被引：4

作者：

Mekonnen, Daniel ^{[1
,2
]}

Munshea, Abaineh ^{[2
,3
]}

Nibret, Endalkachew ^{[2
,3
]}

Adnew, Bethlehem ^{[4
]}

Getachew, Hailu ^{[5
]}

Kebede, Amiro ^{[5
]}

Gebrewahid, Ananya ^{[5
]}

Herrera-Leon, Silvia ^{[6
]}

Amor Aramendia, Aranzazu ^{[7
]}

Benito, Agustin ^{[8
]}

Abascal, Estefania ^{[6
]}

Jacqueline, Camille ^{[6
,9
]}

Aseffa, Abraham ^{[4
]}

Herrera-Leon, Laura ^{[6
,10
]}

机构：

[1] Bahir Dar Univ, Sch Hlth Sci, Dept Med Lab Sci, Coll Med & Hlth Sci, Bahir Dar, Ethiopia

[2] Bahir Dar Univ, Inst Biotechnol, Hlth Biotechnol Div, Bahir Dar, Ethiopia

[3] Bahir Dar Univ, Dept Biol, Bahir Dar, Ethiopia

[4] Armauer Hansen Res Inst, Addis Ababa, Ethiopia

[5] Amhara Publ Hlth Inst, Bahir Dar, Ethiopia

[6] Inst Salud Carlos III, Natl Ctr Microbiol, Madrid, Spain

[7] Fdn Mundo Sano, Madrid, Spain

[8] Inst Hlth Carlos III, Ctr Invest Biomed Red Enfermedades Infecci, Natl Ctr Trop Med, Madrid, Spain

[9] European Ctr Dis Prevent & Control, European Publ Hlth Microbiol Training Programme, Stockholm, Sweden

[10] CIBER Epidemiol Salud Publ, Madrid, Spain

来源：

INFECTION AND DRUG RESISTANCE | 2023年 / 16卷

关键词：

Mycobacterium tuberculosis; L.4.2.2; SIT149; drug resistance; Ethiopia; STREPTOMYCIN RESISTANCE; EVOLUTION; MUTATIONS; PULMONARY; DIVERSITY;

D O I：

10.2147/IDR.S429001

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Introduction: Drug resistance (DR) in Mycobacterium tuberculosis complex (MTBC) is mainly associated with certain lineages and varies across regions and countries. The Beijing genotype is the leading resistant lineage in Asia and western countries. M. tuberculosis (Mtb) (sub) lineages responsible for most drug resistance in Ethiopia are not well described. Hence, this study aimed to identify the leading drug resistance sub-lineages and characterize first-line anti-tuberculosis drug resistance-associated single nucleotide polymorphisms (SNPs). Methods: A facility-based cross-sectional study was conducted in 2020-2022 among new and presumptive multidrug resistant-TB (MDR-TB) cases in Northwest Ethiopia. Whole-genome sequencing (WGS) was performed on 161 isolates using Illumina NovaSeq 6000 technology. The SNP mutations associated with drug resistance were identified using MtbSeq and TB profiler Bioinformatics softwares. Results: Of the 146 Mtb isolates that were successfully genotyped, 20 (13.7%) harbored one or more resistance-associated SNPs. L4.2.2.ETH was the leading drug-resistant sub-lineage, accounting for 10/20 (50%) of the resistant Mtb. MDR-TB isolates showed extensive mutations against first-line anti-TB drugs. Ser450Leu/(tcg/tTg) for Rifampicin (RIF), Ser315Thr/(agc/aCc) for Isoniazid (INH), Met306Ile/(atg/atA(C)) for Ethambutol (EMB), and Gly69Asp for Streptomycin (STR) were the leading resistance associated mutations which accounted for 56.5%, 89.5%, 47%, and 29.4%, respectively. The presence of both clustered and non-clustered drug resistance (DR) isolates indicated that the epidemics is driven by both new DR development and acquired resistance. Conclusion: The high prevalence of drug-resistant TB due to geographically restricted sub-lineages (L4.2.2.ETH) indicates the ongoing local micro epidemics. The Mtb drug resistance surveillance system must be improved. Further evolutionary analysis of L4.2.2.ETH strain is highly desirable to understand evolutionary forces that leads L4.2.2.ETH in to high level DR and transmissible sub-lineage.

引用

页码：6859 / 6870

页数：12