title: Pan-genome multilocus sequence typing and outbreak-specific reference-based single nucleotide polymorphism analysis to resolve two concurrent Staphylococcus aureus outbreaks in neonatal services.
abstract: We used a two-step whole genome sequencing analysis for resolving two concurrent outbreaks in two neonatal services in Belgium, caused by exfoliative toxin A-encoding-gene-positive (eta+) methicillin-susceptible Staphylococcus aureus with an otherwise sporadic spa-type t209 (ST-109). Outbreak A involved 19 neonates and one healthcare worker in a Brussels hospital from May 2011 to October 2013. After a first episode interrupted by decolonization procedures applied over 7 months, the outbreak resumed concomitantly with the onset of outbreak B in a hospital in Asse, comprising 11 neonates and one healthcare worker from mid-2012 to January 2013. Pan-genome multilocus sequence typing, defined on the basis of 42 core and accessory reference genomes, and single-nucleotide polymorphisms mapped on an outbreak-specific de novo assembly were used to compare 28 available outbreak isolates and 19 eta+/spa-type t209 isolates identified by routine or nationwide surveillance. Pan-genome multilocus sequence typing showed that the outbreaks were caused by independent clones not closely related to any of the surveillance isolates. Isolates from only ten cases with overlapping stays in outbreak A, including four pairs of twins, showed no or only a single nucleotide polymorphism variation, indicating limited sequential transmission. Detection of larger genomic variation, even from the start of the outbreak, pointed to sporadic seeding from a pre-existing exogenous source, which persisted throughout the whole course of outbreak A. Whole genome sequencing analysis can provide unique fine-tuned insights into transmission pathways of complex outbreaks even at their inception, which, with timely use, could valuably guide efforts for early source identification.
authors.affiliation: Erasme Hospital, ULB, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Roisin
authors.affiliation: Genoscreen, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Gaudin
authors.affiliation: Erasme Hospital, ULB, Brussels, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: De Mendonça
authors.affiliation: Onze-Lieve-Vrouw hospital, Aalst, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Bellon
authors.affiliation: Onze-Lieve-Vrouw hospital, Aalst, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Van Vaerenbergh
authors.affiliation: Applied Maths, Sint-Martens-Latem, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: De Bruyne
authors.affiliation: Erasme Hospital, ULB, Brussels, Belgium; Ecole de santé publique, ULB, Brussels, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Byl
authors.affiliation: Applied Maths, Sint-Martens-Latem, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Pouseele
authors.affiliation: Erasme Hospital, ULB, Brussels, Belgium; Ecole de santé publique, ULB, Brussels, Belgium.
authors.forename: O
authors.initials: O
authors.lastname: Denis
authors.affiliation: Genoscreen, Lille, France; INSERM U1019, Lille, France; CNRS UMR 8204, Lille, France; Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France; Université de Lille, Lille, France. Electronic address: philip.supply@ibl.cnrs.fr.
authors.forename: P
authors.initials: P
authors.lastname: Supply
mesh_terms: D001530:Belgium / Q000453:epidemiology; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D004196:Disease Outbreaks; D016680:Genome, Bacterial; D006761:Hospitals; D006801:Humans; D007231:Infant, Newborn; D017720:Molecular Epidemiology; D058885:Multilocus Sequence Typing; D020641:Polymorphism, Single Nucleotide; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification
keywords: De novo assembly; Staphylococcus aureus; multilocus sequence typing; neonatal; nosocomial outbreaks; pan-genome; single nucleotide polymorphism; spa-typing; whole genome sequencing