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Open AccessArticle

Whole Genome Sequencing Results Associated with Minimum Inhibitory Concentrations of 14 Anti-Tuberculosis Drugs among Rifampicin-Resistant Isolates of Mycobacterium Tuberculosis from Iran

1
Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran 1417653911, Iran
2
Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran 1417653911, Iran
3
Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
4
Thoracic Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 1417653911, Iran
5
Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran 1417653911, Iran
6
Tehran Regional Reference Laboratory for Tuberculosis, Tehran University of Medical Sciences, Tehran 1417653911, Iran
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(2), 465; https://doi.org/10.3390/jcm9020465
Received: 13 November 2019 / Revised: 15 December 2019 / Accepted: 18 December 2019 / Published: 7 February 2020
(This article belongs to the Special Issue Tuberculosis: Clinical Applications in the Diagnosis and Treatment)
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. View Full-Text
Keywords: Mycobacterium tuberculosis; drug resistance; mutation; gene; minimum inhibitory concentration; whole genome sequencing Mycobacterium tuberculosis; drug resistance; mutation; gene; minimum inhibitory concentration; whole genome sequencing
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MDPI and ACS Style

Kardan-Yamchi, J.; Kazemian, H.; Battaglia, S.; Abtahi, H.; Rahimi Foroushani, A.; Hamzelou, G.; Cirillo, D.M.; Ghodousi, A.; Feizabadi, M.M. Whole Genome Sequencing Results Associated with Minimum Inhibitory Concentrations of 14 Anti-Tuberculosis Drugs among Rifampicin-Resistant Isolates of Mycobacterium Tuberculosis from Iran. J. Clin. Med. 2020, 9, 465. https://doi.org/10.3390/jcm9020465

AMA Style

Kardan-Yamchi J, Kazemian H, Battaglia S, Abtahi H, Rahimi Foroushani A, Hamzelou G, Cirillo DM, Ghodousi A, Feizabadi MM. Whole Genome Sequencing Results Associated with Minimum Inhibitory Concentrations of 14 Anti-Tuberculosis Drugs among Rifampicin-Resistant Isolates of Mycobacterium Tuberculosis from Iran. Journal of Clinical Medicine. 2020; 9(2):465. https://doi.org/10.3390/jcm9020465

Chicago/Turabian Style

Kardan-Yamchi, Jalil; Kazemian, Hossein; Battaglia, Simone; Abtahi, Hamidreza; Rahimi Foroushani, Abbas; Hamzelou, Gholamreza; Cirillo, Daniela M.; Ghodousi, Arash; Feizabadi, Mohammad M. 2020. "Whole Genome Sequencing Results Associated with Minimum Inhibitory Concentrations of 14 Anti-Tuberculosis Drugs among Rifampicin-Resistant Isolates of Mycobacterium Tuberculosis from Iran" J. Clin. Med. 9, no. 2: 465. https://doi.org/10.3390/jcm9020465

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