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Whole Genome Sequencing Results Associated With Minimum Inhibitory Concentrations of 14 Anti-Tuberculosis Drugs Among Rifampicin-Resistant Isolates of Mycobacterium Tuberculosis From Iran Publisher



Kardanyamchi J1, 2 ; Kazemian H2 ; Battaglia S3 ; Abtahi H4 ; Foroushani AR5 ; Hamzelou G6 ; Cirillo DM3 ; Ghodousi A3 ; Feizabadi MM2, 4
Authors
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Authors Affiliations
  1. 1. Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, 1417653911, Iran
  2. 2. Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, 1417653911, Iran
  3. 3. Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
  4. 4. Thoracic Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, 1417653911, Iran
  5. 5. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, 1417653911, Iran
  6. 6. Tehran Regional Reference Laboratory for Tuberculosis, Tehran University of Medical Sciences, Tehran, 1417653911, Iran

Source: Journal of Clinical Medicine Published:2020


Abstract

Accurate and timely detection of drug resistance can minimize the risk of further resistance development and lead to effective treatment. The aim of this study was to determine the resistance to first/second-line anti-tuberculosis drugs in rifampicin/multidrug-resistant Mycobacterium tuberculosis (RR/MDR-MTB) isolates. Molecular epidemiology of strains was determined using whole genome sequencing (WGS)-based genotyping. A total of 35 RR/MDR-MTB isolates were subjected to drug susceptibility testing against first/second-line drugs using 7H9 Middlebrook in broth microdilution method. Illumina technology was used for paired-end WGS applying a Maxwell 16 Cell DNA Purification kit and the NextSeq platform. Data analysis and single nucleotide polymorphism calling were performed using MTBseq pipeline. The genome-based resistance to each drug among the resistant phenotypes was as follows: rifampicin (97.1%), isoniazid (96.6%), ethambutol (100%), levofloxacin (83.3%), moxifloxacin (83.3%), amikacin (100%), kanamycin (100%), capreomycin (100%), prothionamide (100%), D-cycloserine (11.1%), clofazimine (20%), bedaquiline (0.0%), and delamanid (44.4%). There was no linezolid-resistant phenotype, and a bedaquiline-resistant strain was wild type for related genes. The Beijing, Euro-American, and Delhi-CAS were the most populated lineage/sublineages. Drug resistance-associated mutations were mostly linked to minimum inhibitory concentration results. However, the role of well-known drug-resistant genes for D-cycloserine, clofazimine, bedaquiline, and delamanid was found to be more controversial. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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