Evidence map›Paper›PMID 24778110›Full record

ArticleInfection and immunity2014

Origins of a 350-kilobase genomic duplication in Mycobacterium tuberculosis and its impact on virulence.

Pilar Domenech, Anya Rog, Jalal-ud-din Moolji, Nicolas Radomski, Ashley Fallow, Lizbel Leon-Solis, Julia Bowes, Marcel A Behr, Michael B Reed

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. The chosen few:Frontiers in immunology · 2024
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  8. Effects of Host, Sample, andFrontiers in genetics · 2019
    Article
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  11. Article
  12. Article
  13. Review
  14. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Pilar DomenechResearch Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Anya RogResearch Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Jalal-ud-din MooljiResearch Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Nicolas RadomskiResearch Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Ashley FallowResearch Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Lizbel Leon-SolisResearch Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Julia BowesResearch Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Marcel A BehrResearch Institute of the McGill University Health Centre, Montreal, Quebec, Canada McGill International TB Centre, Montreal, Quebec, Canada.
Michael B ReedResearch Institute of the McGill University Health Centre, Montreal, Quebec, Canada McGill International TB Centre, Montreal, Quebec, Canada michael.reed@mcgill.ca.
McGill University Health Centre · CA

Funding

Canadian Institutes of Health Research MOP115133Canadian Institutes of Health Research MOP82931
6 · The paper itself

Abstract

In the present study, we have investigated the evolution and impact on virulence of a 350-kb genomic duplication present in the most recently evolved members of the Mycobacterium tuberculosis East Asian lineage. In a mouse model of infection, comparing HN878 subclones HN878-27 (no duplication) and HN878-45 (with the 350-kb duplication) revealed that the latter is impaired for in vivo growth during the initial 3 weeks of infection. Furthermore, the median survival time of mice infected with isolate HN878-45 is significantly longer (77 days) than that of mice infected with HN878-27. Whole-genome sequencing of both isolates failed to reveal any mutational events other than the duplication that could account for such a substantial difference in virulence. Although we and others had previously speculated that the 350-kb duplication arose in response to some form of host-applied selective pressure (P. Domenech, G. S. Kolly, L. Leon-Solis, A. Fallow, M. B. Reed, J. Bacteriol. 192: 4562-4570, 2010, and B. Weiner, J. Gomez, T. C. Victor, R. M. Warren, A. Sloutsky, B. B. Plikaytis, J. E. Posey, P. D. van Helden, N. C. Gey van Pittius, M. Koehrsen, P. Sisk, C. Stolte, J. White, S. Gagneux, B. Birren, D. Hung, M. Murray, J. Galagan, PLoS One 7: e26038, 2012), here we show that this large chromosomal amplification event is very rapidly selected within standard in vitro broth cultures in a range of isolates. Indeed, subclones harboring the duplication were detectable after just five rounds of in vitro passage. In contrast, the duplication appears to be highly unstable in vivo and is negatively selected during the later stages of infection in mice. We believe that the rapid in vitro evolution of M. tuberculosis is an underappreciated aspect of its biology that is often ignored, despite the fact that it has the potential to confound the data and conclusions arising from comparative studies of isolates at both the genotypic and phenotypic levels.

Indexed as

AnimalsFemaleGene DuplicationGene Expression Regulation, BacterialMiceMycobacterium tuberculosisTuberculosisVirulence

Identifiers

PMID24778110
PMCPMC4097636
OpenAlexW2159877077

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.