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Virulence and antibiotic resistance plasticity of Arcobacter butzleri: Insights on the genomic diversity of an emerging human pathogen

2020Journal article Restricted access
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dc.contributor.authorIsidro, Joana
dc.contributor.authorFerreira, Susana
dc.contributor.authorPinto, Miguel
dc.contributor.authorDomingues, F. C.
dc.contributor.authorOleastro, Mónica
dc.contributor.authorGomes, João Paulo
dc.contributor.authorBorges, Vítor
dc.date.accessioned2020-03-31T08:58:59Z
dc.date.available2020-03-31T08:58:59Z
dc.date.issued2020
dc.description.abstractArcobacter butzleri is a foodborne emerging human pathogen, frequently displaying a multidrug resistant character. Still, the lack of comprehensive genome-scale comparative analysis has limited our knowledge on A. butzleri diversification and pathogenicity. Here, we performed a deep genome analysis of A. butzleri focused on decoding its core- and pan-genome diversity and specific genetic traits underlying its pathogenic potential and diverse ecology. A. butzleri (genome size 2.07-2.58 Mbp) revealed a large open pan-genome with 7474 genes (about 50% being singletons) and a small but diverse core-genome with 1165 genes. It presents a plastic virulome (including newly identified determinants), marked by the differential presence of multiple adaptation-related virulence factors, such as the urease cluster ureD(AB)CEFG (phenotypically confirmed), the hypervariable hemagglutinin-encoding hecA, a type I secretion system (T1SS) harboring another agglutinin and a novel VirB/D4 T4SS likely linked to interbacterial competition and cytotoxicity. In addition, A. butzleri harbors a large repertoire of efflux pumps (EPs) and other antibiotic resistant determinants. We unprecedentedly describe a genetic mechanism of A. butzleri macrolides resistance, (inactivation of a TetR repressor likely regulating an EP). Fluoroquinolones resistance correlated with Thr-85-Ile in GyrA and ampicillin resistance was linked to an OXA-15-like β-lactamase. Remarkably, by decoding the polymorphism pattern of the main antigen PorA, we show that A. butzleri is able to exchange porA as a whole and/or hypervariable epitope-encoding regions separately, leading to a multitude of chimeric PorA presentations that can impact pathogen-host interaction during infection. Ultimately, our unprecedented screening of short sequence repeats indicates that phase variation likely modulates A. butzleri key adaptive functions. In summary, this study constitutes a turning point on A. butzleri comparative genomics revealing that this human gastrointestinal pathogen is equipped with vast and diverse virulence and antibiotic resistance arsenals that open a multitude of phenotypic fingerprints for environmental/host adaptation and pathogenicity.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.meegid.2020.104213pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/10253
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationHealth Sciences Research Centre
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S1567134820300459pt_PT
dc.subjectArcobacter butzleript_PT
dc.subjectGenome diversitypt_PT
dc.subjectVirulence factorspt_PT
dc.subjectAntibiotic resistancept_PT
dc.subjectporApt_PT
dc.subjectPhase variationpt_PT
dc.titleVirulence and antibiotic resistance plasticity of Arcobacter butzleri: Insights on the genomic diversity of an emerging human pathogenpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleHealth Sciences Research Centre
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F00709%2F2019/PT
oaire.citation.startPage104213pt_PT
oaire.citation.titleInfection, Genetics and Evolutionpt_PT
oaire.citation.volume80pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameIsidro
person.familyNameFerreira
person.familyNameDomingues
person.familyNameOleastro
person.givenNameJoana
person.givenNameSusana
person.givenNameFernanda
person.givenNameMónica
person.identifier269435
person.identifier.ciencia-id5413-98F8-F069
person.identifier.ciencia-idF718-3569-E911
person.identifier.ciencia-id6514-0498-3E8F
person.identifier.ciencia-id4115-04A9-FBCB
person.identifier.orcid0000-0002-8529-9878
person.identifier.orcid0000-0001-8308-2862
person.identifier.orcid0000-0002-9540-0853
person.identifier.orcid0000-0001-6360-2576
person.identifier.ridA-6810-2016
person.identifier.ridN-7295-2013
person.identifier.scopus-author-id34874668400
person.identifier.scopus-author-id10139481400
person.identifier.scopus-author-id6603067224
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctCopyright cedido à editora no momento da publicaçãopt_PT
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
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