ArticlePloS one2017
Convergent evolution and topologically disruptive polymorphisms among multidrug-resistant tuberculosis in Peru.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
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- The recent rapid expansion of multidrug resistant Ural lineage Mycobacterium tuberculosis in Moldova.Nature communications · 2024Article
- Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis.Genome medicine · 2024Article
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- Distribution and origins ofMicrobial genomics · 2023Article
- A case report of transmission and disease caused by Mycobacterium caprae and Mycobacterium bovis in Lima, Peru.BMC infectious diseases · 2021Article
- Genomic signatures of pre-resistance in Mycobacterium tuberculosis.Nature communications · 2021Article
- Whole genome analysis of extensively drug resistant Mycobacterium tuberculosis strains in Peru.Scientific reports · 2021Article
- Stepwise pathogenic evolution ofScience (New York, N.Y.) · 2021Article
- Community transmission of multidrug-resistant tuberculosis is associated with activity space overlap in Lima, Peru.BMC infectious diseases · 2021Article
- MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era.Genome medicine · 2020Article
- Association between bacterial homoplastic variants and radiological pathology in tuberculosis.Thorax · 2020Article
- Population structure and genetic diversity of Mycobacterium tuberculosis in Ecuador.Scientific reports · 2020Article
- Exploiting Homoplasy in Genome-Wide Association Studies to Enhance Identification of Antibiotic-Resistance Mutations in Bacterial Genomes.Evolutionary bioinformatics online · 2020Article
- HomoplasyFinder: a simple tool to identify homoplasies on a phylogeny.Microbial genomics · 2019Article
- Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations inInternational journal of mycobacteriologyArticle
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundMultidrug-resistant tuberculosis poses a major threat to the success of tuberculosis control programs worldwide. Understanding how drug-resistant tuberculosis evolves can inform the development of new therapeutic and preventive strategies.
methodsHere, we use novel genome-wide analysis techniques to identify polymorphisms that are associated with drug resistance, adaptive evolution and the structure of the phylogenetic tree. A total of 471 samples from different patients collected between 2009 and 2013 in the Lima suburbs of Callao and Lima South were sequenced on the Illumina MiSeq platform with 150bp paired-end reads. After alignment to the reference H37Rv genome, variants were called using standardized methodology. Genome-wide analysis was undertaken using custom written scripts implemented in R software.
resultsHigh quality homoplastic single nucleotide polymorphisms were observed in genes known to confer drug resistance as well as genes in the Mycobacterium tuberculosis ESX secreted protein pathway, pks12, and close to toxin/anti-toxin pairs. Correlation of homoplastic variant sites identified that many were significantly correlated, suggestive of epistasis. Variation in genes coding for ESX secreted proteins also significantly disrupted phylogenetic structure. Mutations in ESX genes in key antigenic epitope positions were also found to disrupt tree topology.
conclusionVariation in these genes have a biologically plausible effect on immunogenicity and virulence. This makes functional characterization warranted to determine the effects of these polymorphisms on bacterial fitness and transmission.
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