title: Whole-genome analysis of Exserohilum rostratum from an outbreak of fungal meningitis and other infections.
abstract: Exserohilum rostratum was the cause of most cases of fungal meningitis and other infections associated with the injection of contaminated methylprednisolone acetate produced by the New England Compounding Center (NECC). Until this outbreak, very few human cases of Exserohilum infection had been reported, and very little was known about this dematiaceous fungus, which usually infects plants. Here, we report using whole-genome sequencing (WGS) for the detection of single nucleotide polymorphisms (SNPs) and phylogenetic analysis to investigate the molecular origin of the outbreak using 22 isolates of E. rostratum retrieved from 19 case patients with meningitis or epidural/spinal abscesses, 6 isolates from contaminated NECC vials, and 7 isolates unrelated to the outbreak. Our analysis indicates that all 28 isolates associated with the outbreak had nearly identical genomes of 33.8 Mb. A total of 8 SNPs were detected among the outbreak genomes, with no more than 2 SNPs separating any 2 of the 28 genomes. The outbreak genomes were separated from the next most closely related control strain by ∼136,000 SNPs. We also observed significant genomic variability among strains unrelated to the outbreak, which may suggest the possibility of cryptic speciation in E. rostratum.
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA frq8@cdc.gov.
authors.forename: Anastasia P
authors.initials: AP
authors.lastname: Litvintseva
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Hurst
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Lalitha
authors.initials: L
authors.lastname: Gade
authors.affiliation: Biotechnology Core Facility, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Frace
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: Remy
authors.initials: R
authors.lastname: Hilsabeck
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Schupp
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Gillece
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: Chandler
authors.initials: C
authors.lastname: Roe
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: David
authors.initials: D
authors.lastname: Smith
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Keim
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Lockhart
authors.affiliation: Office of the Director, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Shankar
authors.initials: S
authors.lastname: Changayil
authors.affiliation: Office of the Director, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: M Ryan
authors.initials: MR
authors.lastname: Weil
authors.affiliation: Office of the Director, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Duncan R
authors.initials: DR
authors.lastname: MacCannell
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Brandt
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Engelthaler
mesh_terms: D001203:Ascomycota / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D016000:Cluster Analysis; D004196:Disease Outbreaks; D016681:Genome, Fungal; D006801:Humans; D016921:Meningitis, Fungal / Q000453:epidemiology* / Q000382:microbiology; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D058889:Molecular Typing; D016533:Mycological Typing Techniques; D009181:Mycoses / Q000453:epidemiology* / Q000382:microbiology; D009511:New England; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA