Convergent evolution and topologically disruptive polymorphisms among multidrug-resistant tuberculosis in Peru

Grandjean, Louis; Gilman, Robert H.; Iwamoto, Tomotada; Köser, Claudio U.; Coronel, Jorge; Zimic, Mirko; Török, M. Estée; Ayabina, Diepreye; Kendall, Michaela; Fraser, Christophe; Harris, Simon R.; Parkhill, Julian; Peacock, Sharon J.; Moore, David; Colijn, Caroline

doi:10.1371/journal.pone.0189838

Cited by 25 publications

(37 citation statements)

References 44 publications

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“…Since WGS and MIRU-VNTR are very different technologies and MIRU-VNTR samples repetitive regions of the genome that are difficult to capture with short read sequencing, it is natural to expect that trees produced by these input types will differ. This hypothesis is supported by the findings of various studies [5,43,14,18]. Our methods enable us to quantify and visualise such tree differences.…”

Section: Comparing Miru and Wgs Trees Of Mycobacterium Tuberculosissupporting

confidence: 72%

“…We demonstrated one application for M. tuberculosis, comparing the phylogenetic signals from MIRU and WGS data. MIRU typing has been noted to be discordant with WGS for tuberculosis previously [5,43,14,18]; our method can assess this quantitatively. This could form a basis for assessing candidate typing schemes, allowing researchers to seek a scheme with the most reliable and high concordance to core genome phylogenies derived from WGS.…”

Section: Discussionmentioning

confidence: 90%

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Comparing phylogenetic trees according to tip label categories

Kendall

Eldholm

Colijn

2018

Preprint

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Trees that illustrate patterns of ancestry and evolution are a central tool in many areas of biology. Comparing evolutionary trees to each other has widespread applications in comparing the evolutionary stories told by different sources of data, assessing the quality of inference methods, and highlighting areas where patterns of ancestry are uncertain. While these tasks are complicated by the fact that trees are high-dimensional structures encoding a large amount of information, there are a number of metrics suitable for comparing evolutionary trees whose tips have the same set of unique labels. There are also metrics for comparing trees where there is no relationship between their labels: in 'unlabelled' tree metrics the tree shapes are compared without reference to the tip labels.In many interesting applications, however, the taxa present in two or more trees are related but not identical, and it is informative to compare the trees whilst retaining information about their tips' relationships. We present methods for comparing trees whose labels belong to a pre-defined set of categories. The methods include a measure of distance between two such trees, and a measure of concordance between one such tree and a hierarchical classification tree of the unique categories. We demonstrate the intuition of our methods with some toy examples before presenting an analysis of Mycobacterium tuberculosis trees, in which we use our methods to quantify the differences between trees built from typing versus sequence data.

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Section: Comparing Miru and Wgs Trees Of Mycobacterium Tuberculosissupporting

confidence: 72%

Section: Discussionmentioning

confidence: 90%

Comparing phylogenetic trees according to tip label categories

Kendall

Eldholm

Colijn

2018

Preprint

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“…Four genomes from other sources (EMBL-EBI European Nucleotide Archive sequence read archive [study accession IDs: PRJNA393767 [12], PRJEB20942 [13], PRJEB5280 [14], and PRJNA395592 [15]]) were used to demonstrate that the Rv0678 N98D, G121R, and M146T mutations were homoplastic (Additional file 1: Table S1) [16,17].…”

Section: Strain Collections Collectionmentioning

confidence: 99%

MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era

et al. 2020

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Background Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini. Methods We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017). Results MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2. Conclusion The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.

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“…the resistance phenotypes with convergent mutations or homoplastic single nucleotide polymorphisms (SNPs). These mutations in the Mtb isolates would be expected to enhance survival in the presence of anti-TB drugs [14][15][16][17][18] . In addition, associations have been found between homoplastic mutations with increased Mtb transmission rate 19 and TB disease phenotypes, such as tuberculous meningitis 20 .…”

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confidence: 99%

Homoplastic single nucleotide polymorphisms contributed to phenotypic diversity in Mycobacterium tuberculosis

Tantivitayakul

Ruangchai

Juthayothin

et al. 2020

Sci Rep

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Homoplastic mutations are mutations independently occurring in different clades of an organism. The homoplastic changes may be a result of convergence evolution due to selective pressures. Reports on the analysis of homoplastic mutations in Mycobacterium tuberculosis have been limited. Here we characterized the distribution of homoplastic single nucleotide polymorphisms (SNPs) among genomes of 1,170 clinical M. tuberculosis isolates. They were present in all functional categories of genes, with pe/ppe gene family having the highest ratio of homoplastic SNPs compared to the total SNPs identified in the same functional category. Among the pe/ppe genes, the homoplastic Snps were common in a relatively small number of homologous genes, including ppe18, the protein of which is a component of a promising candidate vaccine, M72/AS01E. The homoplastic SNPs in ppe18 were particularly common among M. tuberculosis Lineage 1 isolates, suggesting the need for caution in extrapolating the results of the vaccine trial to the population where L1 is endemic in Asia. As expected, homoplastic SNPs strongly associated with drug resistance. Most of these mutations are already well known. However, a number of novel mutations associated with streptomycin resistance were identified, which warrants further investigation. A SNP in the intergenic region upstream of Rv0079 (DATIN) was experimentally shown to increase transcriptional activity of the downstream gene, suggesting that intergenic homoplastic SNPs should have effects on the physiology of the bacterial cells. Our study highlights the potential of homoplastic mutations to produce phenotypic changes. Under selective pressure and during interaction with the host, homoplastic mutations may confer advantages to M. tuberculosis and deserve further characterization. Mycobacterium tuberculosis (Mtb) is a successful human-adapted species that has undergone long-term coevolution with its human host 1. Previous studies 2,3 revealed the clonal expansion of Mtb, indicating a very low possibility of horizontal gene transfer between strains. Therefore, genetic variations in Mtb appear to be primarily derived from nucleotide substitutions, insertions, and deletions 4,5. The global population of M. tuberculosis sensu stricto is grouped into five phylogenetic lineages, including L1 (Indo-Oceanic family); L2 (East Asian family); L3 (East-African Indian family); L4 (Euro-American); and L7 6,7. In the past decade, several studies have demonstrated associations between Mtb lineages with demographic profiles, geographic distribution, transmission capacity, pathogenesis, cytokine induction, and drug resistance 6,8-10 .Once a strong association has been established, it may be explained through the identification of genotype-specific mutations, in coding or intergenic regions 11-13. Some phenotypes, such as drug resistance, usually occur in several phylogenetic lineages. Mutations that promote drug resistance can be identified by correlating

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Convergent evolution and topologically disruptive polymorphisms among multidrug-resistant tuberculosis in Peru

Cited by 25 publications

References 44 publications

Comparing phylogenetic trees according to tip label categories

Comparing phylogenetic trees according to tip label categories

MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era

Homoplastic single nucleotide polymorphisms contributed to phenotypic diversity in Mycobacterium tuberculosis

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