Whole genome analysis of Exserohilum rostratum from the outbreak of fungal meningitis and other infections.

Litvintseva AP1, Hurst S2, Gade L2, Frace MA3, Hilsabeck R4, Schupp JM4, Gillece JD4, Roe C4, Smith D4, Keim P4, Lockhart SR2, Changayil S5, Weil MR5,MacCannell DR5, Brandt ME2, Engelthaler DM4.

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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 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 detection of single nucleotide polymorphisms (SNP) and phylogenetic analysis to investigate molecular origin of the outbreak using 22 isolates of E. rostratum isolated from 19 case-patients with meningitis or epidural/spinal abscesses, six isolates isolated from contaminated NECC vials, and seven isolates that are 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 eight SNPs were detected among the outbreak genomes, with no more than two SNPs separating any two 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 a possibility of cryptic speciation in E. rostratum.