Abstract
BackgroundCorynebacterium diphtheriae is the main etiological agent of diphtheria, a global disease causing life-threatening infections, particularly in infants and children. Vaccination with diphtheria toxoid protects against infection with potent toxin producing strains. However a growing number of apparently non-toxigenic but potentially invasive C. diphtheriae strains are identified in countries with low prevalence of diphtheria, raising key questions about genomic structures and population dynamics of the species. This study examined genomic diversity among 48 C. diphtheriae isolates collected in Australia over a 12-year period using whole genome sequencing. Phylogeny was determined using SNP-based mapping and genome wide analysis.ResultsC. diphtheriae sequence type (ST) 32, a non-toxigenic clone with evidence of enhanced virulence that has been also circulating in Europe, appears to be endemic in Australia. Isolates from temporospatially related patients displayed the same ST and similarity in their core genomes. The genome-wide analysis highlighted a role of pilins, adhesion factors and iron utilization in infections caused by non-toxigenic strains.ConclusionsThe genomic diversity of toxigenic and non-toxigenic strains of C. diphtheriae in Australia suggests multiple sources of infection and colonisation. Genomic surveillance of co-circulating toxigenic and non-toxigenic C. diphtheriae offer new insights into the evolution and virulence of pathogenic clones and can inform targeted public health actions and policy. The genomes presented in this investigation will contribute to the global surveillance of C. diphtheriae both for the monitoring of antibiotic resistance genes and virulent strains such as those belonging to ST32.
Highlights
Corynebacterium diphtheriae is the main etiological agent of diphtheria, a global disease causing lifethreatening infections, in infants and children
Bacterial isolates and molecular subtyping All C. diphtheriae clinical isolates collected between January 2004 and January 2016 by the Microbial Identification Laboratory New South Wales (NSW) Health Pathology at the Centre for Infectious Diseases and Microbiology, Westmead Hospital were included in the study
Core and accessory genomes of C. diphtheriae strains colonising different ecological niches have significant differences and have virulence mechanisms that modulate their fitness as pathogens
Summary
Corynebacterium diphtheriae is the main etiological agent of diphtheria, a global disease causing lifethreatening infections, in infants and children. A growing number of apparently non-toxigenic but potentially invasive C. diphtheriae strains are identified in countries with low prevalence of diphtheria, raising key questions about genomic structures and population dynamics of the species. Toxin-negative isolates of C. diphtheriae have been revealed to be associated with prosthetic and native valve endocarditis and significantly and more importantly have been increasingly detected in clinical samples [2, 3]. This increase in detection of this bacterium is thought to be due to the uptake of matrix-assisted laser desorption/ ionisation time-of-flight mass spectrometry (MALDI-TOF MS) identification. The growing numbers of emerging non-toxigenic but potentially invasive C. diphtheriae
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