A multiomic approach to defining the essential genome of the globally important pathogen Corynebacterium diphtheriae

Emily C. A. Goodall; Camila Azevedo Antunes; Jens Möller; Vartul Sangal; Von Vergel L. Torres; Jessica Gray; Adam F. Cunningham; Paul A. Hoskisson; Andreas Burkovski; Ian R. Henderson

doi:10.1371/journal.pgen.1010737

A multiomic approach to defining the essential genome of the globally important pathogen Corynebacterium diphtheriae

Emily C. A. Goodall^*, Camila Azevedo Antunes, Jens Möller, Vartul Sangal, Von Vergel L. Torres, Jessica Gray, Adam F. Cunningham, Paul A. Hoskisson, Andreas Burkovski, Ian R. Henderson^*

^*Corresponding author for this work

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Abstract

Author summary Corynebacterium diphtheriae causes both toxin-mediated diphtheria and non-toxigenic invasive infections. Despite a vaccine to protect against diphtheria, case numbers for both invasive and diphtherial disease have increased over the last decade. Furthermore, an increase in antibiotic resistant strains are being isolated from patients. It’s clear that additional treatment strategies for this organism will be needed in the future. Using high-throughput mutagenesis, this work presents the densest library of mutants for any Corynebacterium sp.. This work identifies the essential genome of C. diphtheriae; an important classification as these genes are often the target of therapeutic intervention. We identify highly conserved genes and species-specific genes unique to pathogens. This data presents an important benchmark and focus for the future development of therapeutic options. Of particular significance is the identification of uncharacterized, conserved proteins within the Diphtheria vaccine.

Original language	English
Article number	e1010737
Pages (from-to)	1-29
Number of pages	29
Journal	PLoS Genetics
Volume	19
Issue number	4
DOIs	https://doi.org/10.1371/journal.pgen.1010737
Publication status	Published - 26 Apr 2023

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Goodall, E. C. A., Azevedo Antunes, C., Möller, J., Sangal, V., Torres, V. V. L., Gray, J., Cunningham, A. F., Hoskisson, P. A., Burkovski, A., & Henderson, I. R. (2023). A multiomic approach to defining the essential genome of the globally important pathogen Corynebacterium diphtheriae. PLoS Genetics, 19(4), 1-29. [e1010737]. https://doi.org/10.1371/journal.pgen.1010737

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abstract = "Author summary Corynebacterium diphtheriae causes both toxin-mediated diphtheria and non-toxigenic invasive infections. Despite a vaccine to protect against diphtheria, case numbers for both invasive and diphtherial disease have increased over the last decade. Furthermore, an increase in antibiotic resistant strains are being isolated from patients. It{\textquoteright}s clear that additional treatment strategies for this organism will be needed in the future. Using high-throughput mutagenesis, this work presents the densest library of mutants for any Corynebacterium sp.. This work identifies the essential genome of C. diphtheriae; an important classification as these genes are often the target of therapeutic intervention. We identify highly conserved genes and species-specific genes unique to pathogens. This data presents an important benchmark and focus for the future development of therapeutic options. Of particular significance is the identification of uncharacterized, conserved proteins within the Diphtheria vaccine.",

author = "Goodall, {Emily C. A.} and {Azevedo Antunes}, Camila and Jens M{\"o}ller and Vartul Sangal and Torres, {Von Vergel L.} and Jessica Gray and Cunningham, {Adam F.} and Hoskisson, {Paul A.} and Andreas Burkovski and Henderson, {Ian R.}",

note = "Funding information: PAH would also like to acknowledge funding from Medical Research Scotland (422 FRG) and the Royal Academy of Engineering Research Chair Scheme for long-term personal research support (RCSRF2021\11\15); PAH received a salary from RAEng for this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",

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AU - Möller, Jens

AU - Sangal, Vartul

AU - Torres, Von Vergel L.

AU - Gray, Jessica

AU - Cunningham, Adam F.

AU - Hoskisson, Paul A.

AU - Burkovski, Andreas

AU - Henderson, Ian R.

N1 - Funding information: PAH would also like to acknowledge funding from Medical Research Scotland (422 FRG) and the Royal Academy of Engineering Research Chair Scheme for long-term personal research support (RCSRF2021\11\15); PAH received a salary from RAEng for this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PY - 2023/4/26

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N2 - Author summary Corynebacterium diphtheriae causes both toxin-mediated diphtheria and non-toxigenic invasive infections. Despite a vaccine to protect against diphtheria, case numbers for both invasive and diphtherial disease have increased over the last decade. Furthermore, an increase in antibiotic resistant strains are being isolated from patients. It’s clear that additional treatment strategies for this organism will be needed in the future. Using high-throughput mutagenesis, this work presents the densest library of mutants for any Corynebacterium sp.. This work identifies the essential genome of C. diphtheriae; an important classification as these genes are often the target of therapeutic intervention. We identify highly conserved genes and species-specific genes unique to pathogens. This data presents an important benchmark and focus for the future development of therapeutic options. Of particular significance is the identification of uncharacterized, conserved proteins within the Diphtheria vaccine.

AB - Author summary Corynebacterium diphtheriae causes both toxin-mediated diphtheria and non-toxigenic invasive infections. Despite a vaccine to protect against diphtheria, case numbers for both invasive and diphtherial disease have increased over the last decade. Furthermore, an increase in antibiotic resistant strains are being isolated from patients. It’s clear that additional treatment strategies for this organism will be needed in the future. Using high-throughput mutagenesis, this work presents the densest library of mutants for any Corynebacterium sp.. This work identifies the essential genome of C. diphtheriae; an important classification as these genes are often the target of therapeutic intervention. We identify highly conserved genes and species-specific genes unique to pathogens. This data presents an important benchmark and focus for the future development of therapeutic options. Of particular significance is the identification of uncharacterized, conserved proteins within the Diphtheria vaccine.

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