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

2016-10-17Journal article Restricted access
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dc.contributor.authorPinto, Miguel
dc.contributor.authorBorges, Vítor
dc.contributor.authorAntelo, Minia
dc.contributor.authorPinheiro, Miguel
dc.contributor.authorNunes, Alexandra
dc.contributor.authorAzevedo, Jacinta
dc.contributor.authorBorrego, Maria José
dc.contributor.authorMendonça, Joana
dc.contributor.authorCarpinteiro, Dina
dc.contributor.authorVieira, Luís
dc.contributor.authorGomes, João Paulo.
dc.date.accessioned2016-10-28T10:19:21Z
dc.date.available2016-10-28T10:19:21Z
dc.date.issued2016-10-17
dc.description.abstractInsights 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.pt_PT
dc.description.sponsorshipThis study was partially supported by grant EXPL/BIA-MIC/0309/2013 from the Fundação para a Ciência e a Tecnologia (FCT).pt_PT
dc.identifier.citationNat Microbiol. 2016 Oct 17;2:16190. doi: 10.1038/nmicrobiol.2016.190.pt_PT
dc.identifier.doi10.1038/nmicrobiol.2016.190.pt_PT
dc.identifier.otherESSN: 2058-5276
dc.identifier.urihttp://hdl.handle.net/10400.18/4067
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationNovel approach to "understand" syphilis
dc.relation.publisherversionhttp://www.nature.com/articles/nmicrobiol2016190pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectSyphilispt_PT
dc.subjectTreponema pallidumpt_PT
dc.subjectWithin-patientpt_PT
dc.subjectGenetic Variationpt_PT
dc.subjectPhase Variationpt_PT
dc.subjectTrpKpt_PT
dc.subjectSexually Transmitted Diseasespt_PT
dc.subjectInfectious Diseases
dc.subjectPublic Health
dc.subjectInfecções Sexualmente Transmissíveis
dc.titleGenome-scale analysis of the non-cultivable Treponema pallidum reveals extensive within-patient genetic variationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleNovel approach to "understand" syphilis
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FBIA-MIC%2F0309%2F2013/PT
oaire.citation.titleNature Microbiologypt_PT
oaire.citation.volume2pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctPolítica de copyright e de auto-arquivo do editor.
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication45d2b04a-2c2a-4464-ae80-e3d4fd449f3c
relation.isProjectOfPublication.latestForDiscovery45d2b04a-2c2a-4464-ae80-e3d4fd449f3c

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