Frequency of Mutations Associated with Resistance to First- and Second-Line Drugs in Multidrug Resistant Mycobacterium Tuberculosis Isolates
Abstract
INTRODUCTION: Tuberculosis (TB) is considered one of the most fatal diseases worldwide with an estimation of 10.1 million cases (WHO 2018). In this study, Whole genome sequencing (WGS) was used to perform genomic characterization of 40 Mycobacterium tuberculosis (M. tuberculosis) isolates from patients with different nationalities hospitalized in the Czech Republic.
MATERIALS AND METHODS: Susceptibility testing for first line drugs was performed. DNA was sequenced using Illumina MiSeq platform.
Spoligotypes Single Nucleotide Polymorphisms (SNPs) and mutations in antibiotic resistant genes were detected and phylogenetic analysis was performed. RESULTS: Samples showing phenotypic resistance to at least one drug were 12 to streptomycin, 11 to isoniazid, seven to rifampicin, six to ethambutol and five to pyrazinamide.
Phenotypic and genotypic profiles didn't match in all cases suggesting the presence of novel mutation in some cases and low expression of resistant genes in others. The presented phylogeny enables the correct assignation of M. tuberculosis lineages and sub-lineages.
Our results suggest that the most dominant lineage in our samples was lineages 4 (33/40). CONCLUSION: To our knowledge, this is the first study using this approach to be done in Czech Republic.
Lineage 4 was the predominant lineage identified among our samples. Nevertheless, the dominance of Lineage 4 along with other lineages suggests that infections can be originated from different sources.