Infection and Drug Resistance (Oct 2023)

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

  • Mekonnen D,
  • Munshea A,
  • Nibret E,
  • Adnew B,
  • Getachew H,
  • Kebede A,
  • Gebrewahid A,
  • Herrera-Leon S,
  • Amor Aramendia A,
  • Benito A,
  • Abascal E,
  • Jacqueline C,
  • Aseffa A,
  • Herrera-Leon L

Journal volume & issue
Vol. Volume 16
pp. 6859 – 6870

Abstract

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Daniel Mekonnen,1,2 Abaineh Munshea,2,3 Endalkachew Nibret,2,3 Bethlehem Adnew,4 Hailu Getachew,5 Amiro Kebede,5 Ananya Gebrewahid,5 Silvia Herrera-Leon,6 Aranzazu Amor Aramendia,7 Agustín Benito,8 Estefanía Abascal,6 Camille Jacqueline,6,9 Abraham Aseffa,4 Laura Herrera-Leon6,10 1Department of Medical Laboratory Sciences, School of Health Science, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia; 2Health Biotechnology Division, Institute of Biotechnology, Bahir Dar University, Bahir Dar, Ethiopia; 3Department of Biology, Bahir Dar University, Bahir Dar, Ethiopia; 4Armauer Hansen Research Institute, Addis Ababa, Ethiopia; 5Amhara Public Health Institute, Bahir Dar, Ethiopia; 6National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; 7Fundación Mundo Sano, Madrid, Spain; 8National Center of Tropical Medicine, Institute of Health Carlos III, Centro de Investigación Biomédica En Red de Enfermedades Infecciosas, Madrid, Spain; 9European Public Health Microbiology Training Programme, European Centre for Disease Prevention and Control, Stockholm, Sweden; 10CIBER Epidemiologia y Salud Publica, Madrid, SpainCorrespondence: Daniel Mekonnen, Email [email protected]: 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.Keywords: Mycobacterium tuberculosis, L.4.2.2, SIT149, drug resistance, Ethiopia

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