Analysis of clinical Bordetella pertussis isolates using whole genome sequences reveals novel genomic regions associated with recent outbreaks in the United States of America

Abstract Background:Despite high-levels of vaccination, whooping cough, primarily caused by Bordetella pertussis (BP), has persisted and resurged. It remains a major cause of infant death worldwide and is the most prevalent vaccine-preventable disease in developed countries. To date, most genomic studies have focused on a small subset of the BP genome, biasing our clinical understanding and public health awareness. Methods:We performed a Genome-Wide Association Study (GWAS) on 76 U.S. BP whole genomes, including strains from recent outbreaks. Results:A GWAS of the 76 BP isolates revealed a sharp increase in genetic variation associated with the Minnesota 2012 outbreak and identified 52 variants unique to the Minnesota outbreak and 19 unique to the California and Washington outbreaks. None of the identified variants were shared between the outbreaks and the vast majority were previously uncharacterized. We further identified variation associated with pertactin negative strains and acellular vaccination. Conclusions:We identified novel genomic regions associated with recent BP outbreaks. Our results underscore the need for increased whole genome sequencing of BP isolates, which can reduce costly misdiagnosis and improve surveillance. The genes containing these variants warrant further investigation into their possible roles in BP pathogenicity and the ongoing resurgence in the U.S.