Detection of first and second line drug resistance mutations from multi drug resistantmycobacterium tuberculosisstrains by Ion Torrent whole genome sequencing (WGS)

Autor: Simona Peter, Ionut Pavel, Florin Rusu-Cordunean, Daniela Diculencu, Ina Iuliana Macovei, Bogdan Grigoriu
Rok vydání: 2016
Předmět:
Zdroj: 10.2 Tuberculosis.
Popis: Treatment success in patients infected with multi-drug resistant strains tuberculosis (MDR-TB) depends on the proper drug choice. Molecular biology methods allowed the identification of the genomic resistance profile of Mycobacterium tuberculosis within several days. Aim of the study was to assess the capacity of Ion Torrent WGS technology to identify resistance mutations from Mycobacterium tuberculosis MDR strains using the phenotypic method as a reference. Methods: Sixty two MDR-TB isolates subjected to first and second drug susceptibility testing (DST) using the proportion method, were sequenced on Ion Torrent platform and aligned against H37Rv reference genome. Bioinformatic analysis was performed with SeqNext software; 97 genes known to be involved in resistance to commonly used antituberculous drugs were analyzed. Results: A total number of 216 different mutations were identified on the studied genes. Of these 130 were not yet described in available databases and their significance was not known; 86 were know resistance associated mutation of which 40 being described as confidently associated with resistance. Correlation of genotypic profile with phenotypic data showed the following concordance: MDR-95.2%; INH-96.8%; RIF-98.4%; EMB-86.4%; SM–92.7%; OFX–80%, CAP–100%, KAN–73.3%; XDR–78.6%. Conclusions: Ion Torrent WGS permits a rapid identification of multi-drug resistant strains with known mutations but also identification of novel mutations with possible associations in antibiotic resistance, presenting a high potential for guidance of physicians and reference laboratories.
Databáze: OpenAIRE