title: Co-diversification ofEnterococcus faeciumCore Genomes and PBP5: Evidences ofpbp5Horizontal Transfer.
abstract: Ampicillin resistance has greatly contributed to the recent dramatic increase of a cluster of human adaptedEnterococcus faeciumlineages (ST17, ST18, and ST78) in hospital-based infections. Changes in the chromosomalpbp5gene have been associated with different levels of ampicillin susceptibility, leading to protein variants (designated as PBP5 C-types to keep the nomenclature used in previous works) with diverse degrees of reduction in penicillin affinity. Our goal was to use a comparative genomics approach to evaluate the relationship between the diversity of PBP5 amongE. faeciumisolates of different phylogenomic groups as well as to assess thepbp5transferability among isolates of disparate clonal lineages. The analyses of 78 selectedE. faeciumstrains as well as publishedE. faeciumgenomes, suggested that the diversity ofpbp5mirrors the phylogenomic diversification ofE. faecium. The presence of identical PBP5 C-types as well as similarpbp5genetic environments in differentE. faeciumlineages and clones from quite different geographical and environmental origin was also documented and would indicate their horizontal gene transfer amongE. faeciumpopulations. This was supported by experimental assays showing transfer of large (≈180-280 kb) chromosomal genetic platforms containingpbp5alleles,ponA(transglycosilase) and other metabolic and adaptive features, fromE. faeciumdonor isolates to suitableE. faeciumrecipient strains. Mutation profile analysis of PBP5 from available genomes and strains from this study suggests that the spread of PBP5 C-types might have occurred even in the absence of a significant ampicillin resistance phenotype. In summary, genetic platforms containingpbp5sequences were stably maintained in particularE. faeciumlineages, but were also able to be transferred amongE. faeciumclones of different origins, emphasizing the growing risk of further spread of ampicillin resistance in this nosocomial pathogen.
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade Farmácia, Universidade do Porto Porto, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Novais
authors.affiliation: Servicio de Microbiología, Instituto Ramón y Cajal de Investigación SanitariaMadrid, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud PúblicaBarcelona, Spain.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Tedim
authors.affiliation: Servicio de Microbiología, Instituto Ramón y Cajal de Investigación SanitariaMadrid, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud PúblicaBarcelona, Spain.
authors.forename: Val F
authors.initials: VF
authors.lastname: Lanza
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade Farmácia, Universidade do PortoPorto, Portugal; Servicio de Microbiología, Instituto Ramón y Cajal de Investigación SanitariaMadrid, Spain.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Freitas
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade Farmácia, Universidade do Porto Porto, Portugal.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Silveira
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade Farmácia, Universidade do PortoPorto, Portugal; Faculdade de Ciências da Saúde, Universidade Fernando PessoaPorto, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Escada
authors.affiliation: Division of Microbial Diseases, UCL Eastman Dental Institute, University College London London, UK.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Roberts
authors.affiliation: Division of Microbial Diseases, UCL Eastman Dental Institute, University College London London, UK.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Haroni
authors.affiliation: Servicio de Microbiología, Instituto Ramón y Cajal de Investigación SanitariaMadrid, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud PúblicaBarcelona, Spain; Unidad de Resistencia a Antibióticos y Virulencia Bacteriana (RYC-CSIC)Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Baquero
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade Farmácia, Universidade do Porto Porto, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Peixe
authors.affiliation: Servicio de Microbiología, Instituto Ramón y Cajal de Investigación SanitariaMadrid, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud PúblicaBarcelona, Spain; Unidad de Resistencia a Antibióticos y Virulencia Bacteriana (RYC-CSIC)Madrid, Spain.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Coque
keywords: PBP5 mutations; PonA; ampicillin resistance; chromosomal transfer; phylogenomic diversification