Dados do Trabalho

Título

Epistatic potential between resistance genes and virulence genes in multidrug-resistant Mycobacterium tuberculosis isolates

Introdução

Two major challenges for tuberculosis (TB) control are the spread of multidrug-resistant (MDR) strains and the emergence of extensively resistant (XDR) strains. TB caused by drug-resistant Mycobacterium tuberculosis (MTB) is multifactorial and its rates have increased worldwide, making treatment more difficult, limited and costly. The acquisition of drug resistance results from chromosomal mutations and the genomic mechanisms may be involved in genetic alterations that, in addition, alter the adaptability of MTB. Epistasis or gene interaction occurs when the phenotypic effect of a mutation in a locus depends on mutations present at other loci.Recent studies reveal epistasis between chromosomal mutations that determine resistance and virulence, suggesting an adaptive driving force.

Objetivo(s)

The aim of this study was to identify epistatic genes in genomic virulence islands in MDR isolates.

Material e Métodos

Samples from patients with TB living in Salvador/BA from 2008 to 2011 were phenotypically and genotypically classified. LAM (LatinAmerican-Mediterranean) strain, the most prevalent in Salvador/BA, was analyzed. DNA samples were submitted to Illumina (HiSeq2000 platform). FastQC was used, followed by trimming and filtering of reads in paired-end libraries using Trimmomatic. Genomeswere assembled by Unicycler and SPAdes. The phylogenomic tree was constructed using genomic sequences extracted from NCBIGenBank. BLASTN and iTOL were used to perform comparison and customization. To detect potential epistatic effect, comparisonswere made between resistance genes and virulence genes. The genomes of the MDR isolates and the genome of H37Rv and H37Rawere loaded into the Pathosystems Resource Integration Center (PATRIC) platform.

Resultados e Conclusão

Five clusters were identified by genetic similarity and one subcluster with similarity above 99.91%.
Fifty-five LAM MDRisolates had drug resistance genes from the drugs of TB treatment protocol.
Synonymous and non-synonymous mutations invirulence genes were identified in MDR isolates, suggesting degrees of epistasis between resistance and virulence genes. The results of this study contribute to the knowledge about the molecular epidemiology of TB, in order to broaden the understanding ofthe interaction of MTB with the susceptible host and reflect on the dynamics of transmission of MDR strains.

Palavras-chave

Tuberculosis; Multidrug resistance; Epistasis; Biological fitness