title: Single-Molecule Sequencing (PacBio) of theStaphylococcus capitisNRCS-A Clone Reveals the Basis of Multidrug Resistance and Adaptation to the Neonatal Intensive Care Unit Environment.
abstract: The multi-resistantStaphylococcus capitisclone NRCS-A has recently been described as a major pathogen causing nosocomial, late-onset sepsis (LOS) in preterm neonates worldwide. NRCS-A representatives exhibit an atypical antibiotic resistance profile. Here, the complete closed genome (chromosomal and plasmid sequences) of NRCS-A prototype strain CR01 and the draft genomes of three other clinical NRCS-A strains from Australia, Belgium and the United Kingdom are annotated and compared to available non-NRCS-AS. capitisgenomes. Our goal was to delineate the uniqueness of the NRCS-A clone with respect to antibiotic resistance, virulence factors and mobile genetic elements. We identified 6 antimicrobial resistance genes, all carried by mobile genetic elements. Previously described virulence genes present in the NRCS-A genomes are shared with the six non-NRCS-AS. capitisgenomes. Overall, 63 genes are specific to the NRCS-A lineage, including 28 genes located in the methicillin-resistance cassette SCCmec. Among the 35 remaining genes, 25 are of unknown function, and 9 correspond to an additional type I restriction modification system (n= 3), a cytosine methylation operon (n= 2), and a cluster of genes related to the biosynthesis of teichoic acids (n= 4). Interestingly, a tenth gene corresponds to a resistance determinant for nisin (nsrgene), a bacteriocin secreted by potential NRCS-A strain niche competitors in the gut microbiota. The genomic characteristics presented here emphasize the contribution of mobile genetic elements to the emergence of multidrug resistance in theS. capitisNRCS-A clone. No NRCS-A-specific known virulence determinant was detected, which does not support a role for virulence as a driving force of NRCS-A emergence in NICUs worldwide. However, the presence of a nisin resistance determinant on the NRCS-A chromosome, but not in otherS. capitisstrains and most coagulase-negative representatives, might confer a competitive advantage to NRCS-A strains during the early steps of gut colonization in neonates. This suggests that the striking adaptation of NRCS-A to the NICU environment might be related to its specific antimicrobial resistance and also to a possible enhanced ability to challenge competing bacteria in its ecological niche.
authors.affiliation: Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de LyonLyon, France; International Centre for Research in Infectious Diseases, Institut National de la Santé et de la Recherche Médicale U1111, University of LyonLyon, France; National Reference Center for Staphylococci, Hospices Civils de LyonLyon, France.
authors.forename: Patrícia Martins
authors.initials: PM
authors.lastname: Simões
authors.affiliation: Biotechnology Laboratory (Medbiotech), Medical and Pharmacy School, University Mohammed V de Rabat Rabat, Morocco.
authors.forename: Hajar
authors.initials: H
authors.lastname: Lemriss
authors.affiliation: Department of Clinical Microbiology, Eastern Hospital Group, Hospices Civils de Lyon Lyon, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Dumont
authors.affiliation: Department of Biosecurity PCL3, Laboratory of Research and Medical Analysis of the Fraternal of Gendarmerie Royale Rabat, Morocco.
authors.forename: Sanâa
authors.initials: S
authors.lastname: Lemriss
authors.affiliation: International Centre for Research in Infectious Diseases, Institut National de la Santé et de la Recherche Médicale U1111, University of LyonLyon, France; National Reference Center for Staphylococci, Hospices Civils de LyonLyon, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rasigade
authors.affiliation: Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de LyonLyon, France; International Centre for Research in Infectious Diseases, Institut National de la Santé et de la Recherche Médicale U1111, University of LyonLyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Assant-Trouillet
authors.affiliation: Biotechnology Laboratory (Medbiotech), Medical and Pharmacy School, University Mohammed V de Rabat Rabat, Morocco.
authors.forename: Azeddine
authors.initials: A
authors.lastname: Ibrahimi
authors.affiliation: Department of Biosecurity PCL3, Laboratory of Research and Medical Analysis of the Fraternal of Gendarmerie Royale Rabat, Morocco.
authors.forename: Saâd
authors.initials: S
authors.lastname: El Kabbaj
authors.affiliation: Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de LyonLyon, France; Neonatal Intensive Care Unit, Eastern Hospital Group, Hospices Civils de LyonLyon, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Butin
authors.affiliation: Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de LyonLyon, France; International Centre for Research in Infectious Diseases, Institut National de la Santé et de la Recherche Médicale U1111, University of LyonLyon, France; National Reference Center for Staphylococci, Hospices Civils de LyonLyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laurent
keywords: SMRT; Staphylococcus capitis; bacteremia; comparative genomics; late-onset sepsis; multiple drug resistance; nisin