Stylized DNA strand interwoven with Rio de Janeiro skyline and microscopic bacteria.

Decoding Diphtheria: How Genomic Analysis Helps Us Understand This Threat

"A deep dive into a nontoxigenic strain of Corynebacterium diphtheriae and its implications for public health."


Diphtheria, caused by Corynebacterium diphtheriae, remains a significant public health concern despite widespread immunization programs. While toxigenic strains are well-known, nontoxigenic strains are increasingly recognized for their ability to cause severe invasive infections, such as endocarditis and septic arthritis. These infections are not preventable by traditional vaccines, necessitating a deeper understanding of their genomic characteristics.

Recent outbreaks have highlighted the escalating genomic diversity of C. diphtheriae, emphasizing the need to investigate the plasticity and virulence determinants of these strains. This has prompted researchers to explore the genetic makeup of nontoxigenic strains to identify potential factors contributing to their pathogenicity.

A recent study focused on the genomic sequencing, annotation, and analysis of HC07, a nontoxigenic, invasive C. diphtheriae strain isolated from a patient with endocarditis in Rio de Janeiro, Brazil. This research aims to shed light on the genetic underpinnings that enable these strains to cause severe infections.

Unveiling the Genomic Landscape of HC07

Stylized DNA strand interwoven with Rio de Janeiro skyline and microscopic bacteria.

The HC07 strain, belonging to biotype gravis, was isolated in 2013 and identified through conventional microbiological methods and the API Coryne System. The strain was confirmed to be nontoxigenic via the modified Elek test and Vero cell cytotoxicity assay. Multilocus sequence typing (MLST) revealed that HC07 corresponds to sequence type ST-171, further classifying its genetic profile.

Genomic sequencing of HC07 was performed using an Illumina HiSeq 2500 sequencer, generating a high coverage of the genome. The sequence data was assembled using the A5-miseq pipeline, followed by gene prediction and annotation through the National Center for Biotechnology Information (NCBI) Prokaryotic Genomes Automatic Annotation Pipeline. This comprehensive approach provided a detailed map of the HC07 genome, revealing key insights into its genetic composition.
Key genomic features identified include:
  • Total genome size: 2,491,635 bp
  • GC content: 53.53%
  • Number of genes: 2,333
  • rRNAs: 6 (5S, 16S, 23S) and tRNAs: 51
Phylogenetic analysis, based on concatenated MLST genes, demonstrated that HC07 clusters closely with other nontoxigenic strains, such as HC03 and HC04, isolated from endocarditis patients in Rio de Janeiro. These strains, despite being isolated at different times, share a close genetic relationship, suggesting a persistent lineage in the region. Whole-genome-based phylogeny further supported this close relationship, corroborating previous findings that biovar classification does not always align with the phylogenetic relationships of C. diphtheriae.

Implications for Public Health and Future Research

The genomic analysis of HC07 provides valuable insights into the diversity and plasticity of nontoxigenic C. diphtheriae strains. The presence of specific virulence factors, a unique prophage, and various genomic islands highlights the complex genetic adaptations that contribute to the bacterium's pathogenicity. Further research is needed to fully understand the mechanisms driving the evolution and persistence of these strains and their implications for public health. Continued genomic surveillance and analysis will be crucial in developing effective strategies to combat infections caused by nontoxigenic C. diphtheriae.

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