Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheriae

Robert C Will,Agila Kumari Pragasam,Karthick Vasudevan,Vartul Sangal,Gordon Dougan,Ankur Mutreja,Lucky Sangal,Pradeep Haldar,Thandavarayan Ramamurthy,Naresh Chand Sharma,Dhirendra Kumar,Stephen Baker,Eva Heinz,Vyacheslav Melnikov,Bhabatosh Das,Balaji Veeraraghavan

doi:10.1038/s41467-021-21870-5

Abstract

Diphtheria is a respiratory disease caused by the bacterium Corynebacterium diphtheriae. Although the development of a toxin-based vaccine in the 1930s has allowed a high level of control over the disease, cases have increased in recent years. Here, we describe the genomic variation of 502 C. diphtheriae isolates across 16 countries and territories over 122 years. We generate a core gene phylogeny and determine the presence of antimicrobial resistance genes and variation within the tox gene of 291 tox+ isolates. Numerous, highly diverse clusters of C. diphtheriae are observed across the phylogeny, each containing isolates from multiple countries, regions and time of isolation. The number of antimicrobial resistance genes, as well as the breadth of antibiotic resistance, is substantially greater in the last decade than ever before. We identified and analysed 18 tox gene variants, with mutations estimated to be of medium to high structural impact.

Highlights

Diphtheria is a respiratory disease caused by the bacterium Corynebacterium diphtheriae
We interrogate the genomes of a large collection of C. diphtheriae isolates to determine their phylogenetic structure, assess the presence of antimicrobial resistance (AMR) genes and assess toxin variation, which is the key target of the current diphtheria vaccine
By analysing a large collection of C. diphtheriae genomes we identified numerous clades distributed across the globe

Summary

Introduction

Diphtheria is a respiratory disease caused by the bacterium Corynebacterium diphtheriae. The development of a toxin-based vaccine in the 1930s has allowed a high level of control over the disease, cases have increased in recent years. We describe the genomic variation of 502 C. diphtheriae isolates across 16 countries and territories over 122 years. Once a common cause of infection, diphtheria has been vaccine preventable for decades and is rarely observed in high income countries[2,4]. Non-toxigenic C. diphtheriae can cause disease, often in the form of systemic infections[17,18]. We interrogate the genomes of a large collection of C. diphtheriae isolates to determine their phylogenetic structure, assess the presence of antimicrobial resistance (AMR) genes and assess toxin variation, which is the key target of the current diphtheria vaccine

Methods

Results

Conclusion