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

dc.contributor.authorIsidro, Joana
dc.contributor.authorFerreira, Susana
dc.contributor.authorPinto, Miguel
dc.contributor.authorDomingues, Fernanda
dc.contributor.authorOleastro, Mónica
dc.contributor.authorGomes, João Paulo
dc.contributor.authorBorges, Vítor
dc.date.accessioned2020-04-30T22:15:28Z
dc.date.available2020-04-30T22:15:28Z
dc.date.issued2020-06
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.sponsorshipThis work was partially supported by funds from the Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior (CICS-UBI), through National Funds by FCT - Foundation for Science and Technology (UID/Multi/00709/2019), Portugal.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInfect Genet Evol. 2020 Jun;80:104213. doi: 10.1016/j.meegid.2020.104213. Epub 2020 Jan 30pt_PT
dc.identifier.doi10.1016/j.meegid.2020.104213pt_PT
dc.identifier.issn1567-1348,
dc.identifier.urihttp://hdl.handle.net/10400.18/6570
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S1567134820300459?via%3Dihubpt_PT
dc.subjectAntibiotic Resistancept_PT
dc.subjectArcobacter butzleript_PT
dc.subjectGenome Diversitypt_PT
dc.subjectPhase Variationpt_PT
dc.subjectVirulence Factorspt_PT
dc.subjectporApt_PT
dc.subjectInfecções Gastrointestinaispt_PT
dc.subjectResistência aos Antimicrobianospt_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.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F00709%2F2013/PT
oaire.citation.startPage104213pt_PT
oaire.citation.titleInfection, Genetics and Evolutionpt_PT
oaire.citation.volume80pt_PT
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctDe acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationf5e75317-d96b-4bfe-97b5-3912e4125430
relation.isProjectOfPublication.latestForDiscoveryf5e75317-d96b-4bfe-97b5-3912e4125430

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