AI Article Synopsis

  • - The study focused on analyzing the genetic diversity of Mycobacterium tuberculosis (Mtb) isolates from drug-resistant tuberculosis patients in Brazil, finding a high prevalence of multidrug-resistant cases at 54.8% and pre-extensively drug-resistant cases at 9.2%.
  • - Researchers utilized whole-genome sequencing (WGS) to scrutinize 298 Mtb isolates, identifying the most common sub-lineage as 4.3 and uncovering 20 new mutations linked to drug resistance, with significant ongoing transmission among patients noted through genomic clustering.
  • - The in-house WGS pipeline outperformed online tools in predicting drug resistance, revealing key associations between certain genotypes and severe disease outcomes, which enhances the understanding of

Article Abstract

The present study aimed to determine the genetic diversity of isolates of (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB ( = 0.03) and either phenotypic ( = 0.006) or genotypic ( = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11200758PMC
http://dx.doi.org/10.3390/antibiotics13060496DOI Listing

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