Evolutionary dynamics and genomic features of the Elizabethkingia anophelis Wisconsin outbreak strain

A large outbreak of Elizabethkingia anophelis infections, concentrated in Wisconsin, USA, began in late 2015 and peaked in late February, 2016. To date, the source of E. anophelis and its mode of transmission during the outbreak have not been identified despite extensive epidemiological investigations combined with environmental and product testing. We sequenced the complete genomes of E. anophelis isolates from 59 patients, demonstrating that the outbreak was caused by a single strain. It represents a unique E. anophelis genetic sublineage with thirteen characteristic genomic regions. Strikingly, the outbreak isolates showed substantial genetic diversity (290 single nucleotide polymorphisms), an accelerated evolutionary rate (6.35x10^-6 substitutions per site per year) and an atypical mutational spectrum. Intra-outbreak phylogenetic analysis revealed diversification into six major phylogenetic sub-clusters with distinctive temporal and geographic dynamics. The last common ancestor of all outbreak isolates was estimated to have been present nearly one year before the first human infection, suggesting evolution in the as-yet-unidentified reservoir. Unlike other E. anophelis, the outbreak strain had a disrupted DNA repair mutY gene caused by insertion of an integrative and conjugative element (ICEEa1). This genomic change probably contributed to the high evolutionary rate of the outbreak strain and may have increased its adaptability. Many mutations occurred during the outbreak in protein-coding genes, including positively selected disruptions of polysaccharide utilization and capsule export genes. This unique discovery of an outbreak caused by a naturally occurring mutator bacterial pathogen provides a dramatic example of the potential impact of pathogen evolutionary dynamics on infectious disease epidemiology.