Evidence map›Paper›PMID 27748767›Full record

ArticleNature microbiology2016

Genome-scale analysis of the non-cultivable Treponema pallidum reveals extensive within-patient genetic variation.

Miguel Pinto, Vítor Borges, Minia Antelo, Miguel Pinheiro, Alexandra Nunes, Jacinta Azevedo, Maria José Borrego, Joana Mendonça, Dina Carpinteiro, Luís Vieira and 1 more

Abstract read
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In one paragraph

Article in Nature microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
9.0field-weighted citation impact, top 2% 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

63 citing papers in PubMed, 107 citations in OpenAlex.

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  17. Molecular Capture ofInternational journal of molecular sciences · 2023
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  18. Strengthening the genomic surveillance ofFrontiers in microbiology · 2023
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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Miguel PintoReference Laboratory of Bacterial Sexually Transmitted Infections, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal.
Vítor BorgesReference Laboratory of Bacterial Sexually Transmitted Infections, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal.
Minia AnteloReference Laboratory of Bacterial Sexually Transmitted Infections, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal.
Miguel PinheiroSchool of Medicine, University of St Andrews, KY16 9TF, UK.
Alexandra NunesReference Laboratory of Bacterial Sexually Transmitted Infections, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal.
Jacinta AzevedoSexually Transmitted Diseases Clinic, Lapa Health Centre, 1200-831 Lisbon, Portugal.
Maria José BorregoReference Laboratory of Bacterial Sexually Transmitted Infections, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal.
Joana MendonçaInnovation and Technology Unit, Department of Human Genetics, National Institute of Health, 1649-016 Lisbon, Portugal.
Dina CarpinteiroInnovation and Technology Unit, Department of Human Genetics, National Institute of Health, 1649-016 Lisbon, Portugal.
Luís VieiraInnovation and Technology Unit, Department of Human Genetics, National Institute of Health, 1649-016 Lisbon, Portugal.
João Paulo GomesReference Laboratory of Bacterial Sexually Transmitted Infections, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal.
National Institute of Health Dr. Ricardo Jorge · PTUniversity of St Andrews · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Insights into the genomic adaptive traits of Treponema pallidum, the causative bacterium of syphilis, have long been hampered due to the absence of in vitro culture models and the constraints associated with its propagation in rabbits. Here, we have bypassed the culture bottleneck by means of a targeted strategy never applied to uncultivable bacterial human pathogens to directly capture whole-genome T. pallidum data in the context of human infection. This strategy has unveiled a scenario of discreet T. pallidum interstrain single-nucleotide-polymorphism-based microevolution, contrasting with a rampant within-patient genetic heterogeneity mainly targeting multiple phase-variable loci and a major antigen-coding gene (tprK). TprK demonstrated remarkable variability and redundancy, intra- and interpatient, suggesting ongoing parallel adaptive diversification during human infection. Some bacterial functions (for example, flagella- and chemotaxis-associated) were systematically targeted by both inter- and intrastrain single nucleotide polymorphisms, as well as by ongoing within-patient phase variation events. Finally, patient-derived genomes possess mutations targeting a penicillin-binding protein coding gene (mrcA) that had never been reported, unveiling it as a candidate target to investigate the impact on the susceptibility to penicillin. Our findings decode the major genetic mechanisms by which T. pallidum promotes immune evasion and survival, and demonstrate the exceptional power of characterizing evolving pathogen subpopulations during human infection.

Indexed as

Genetic VariationGenome, BacterialEvolution, MolecularGenomicsHumansPolymorphism, Single NucleotideSyphilisTreponema pallidum

Identifiers

PMID27748767
OpenAlexW2534180353

What OpenQuestion holds

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Registered trials

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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.