Mutations of Mycobacterium tuberculosis induced by anti-tuberculosis treatment result in metabolism changes and elevation of ethambutol resistance.

Mutations of Mycobacterium tuberculosis induced by anti-tuberculosis treatment result in metabolism changes and elevation of ethambutol resistance. Infect Genet Evol. 2018 Oct 03;: Authors: Sun L, Zhang L, Wang T, Jiao W, Li Q, Yin Q, Li J, Qi H, Xu F, Shen C, Xiao J, Liu S, Mokrousov I, Huang H, Shen A Abstract Selective pressure from antibiotic use is one of the most important risk factors associated with the development of drug resistance in Mycobacterium tuberculosis (MTB). However, the mechanisms underlying drug resistance at the molecular level remain partly unclear. Therefore, the purpose of this study was to investigate the potential functional effect of novel mutations arising from anti-tuberculosis treatment. We analyzed two multidrug-resistant TB (MDR-TB) isolates from the same patient; one collected before and one almost a year after commencing MDR-TB treatment. The post-treatment isolate exhibited elevated ethambutol resistance. We sequenced the whole genomes of the two clinical isolates and detected six novel polymorphisms affecting the genes Rv1026, nc0021, Rv2155c, Rv2437, and Rv3696c, and the intergenic region between Rv2764c and Rv2765. Metabolomics approach was used to reveal the effect of the found variation on the metabolic pathways of MTB. Partial least squares-discriminant analysis showed a clear differentiation between the two isolates, involving a total of 175 metabolites. Pathway analysis showed that these m...
Source: Infection, Genetics and Evolution - Category: Genetics & Stem Cells Authors: Tags: Infect Genet Evol Source Type: research