Virulence and mutations analysis based on the whole genome of a Brazilian Corynebacterium diphtheriae strain isolated from a cutaneous infection

<i>Corynebacterium diphtheriae</i> is the main etiological agent of diphtheria, a potentially fatal disease whose most severe signs and symptoms result from the action of an exotoxin, the diphtheria toxin (DT). Although non-toxigenic <i>C. diphtheriae</i> strains have been associated with several diseases, including cutaneous infections and endocarditis, they are not monitored in many countries, and their mechanisms of virulence and antimicrobial resistance remain underexplored. Therefore, this study aimed to provide a comprehensive characterization -through genomic, <i>in vitro</i>, and <i>in vivo</i> analyses - of a non-toxigenic <i>C. diphtheriae</i> strain (46855) isolated from a leg lesion, highlighting its pathogenic potential and resistance profile. The isolate was assigned to a novel sequence type (ST-925) and was found to be resistant to tetracycline and rifampin. Multiple antimicrobial resistance genes were predicted in the genome, such as tet(33), rbpA, and rpoB2, in addition to mutations in the rpoB gene. A diverse set of virulence-associated genes related to adhesion, iron uptake systems, gene regulation, and post-translational modification was also identified. The isolate was able to form biofilm <i>in vitro</i> and exhibited strong virulence in <i>Galleria mellonella</i> larvae and A549 human pneumocyte cells. Finally, the structural analysis of the rpoB gene, carried out for the first time in this study, linked the observed mutations to rifampin resistance in <i>C. diphtheriae</i>. In summary, the data revealed that <i>C. diphtheriae</i> 46855, although non-toxigenic, harbors multiple genes associated with antimicrobial resistance and virulence, emphasizing the need for greater surveillance and functional studies on non-toxigenic strains.

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Journal
Frontiers in Microbiology
Published
2025-10-15
DOI
https://doi.org/10.3389/fmicb.2025.1579154
Primary Topic
Diphtheria, Corynebacterium, and Tetanus
Type
article
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article

Virulence and mutations analysis based on the whole genome of a Brazilian Corynebacterium diphtheriae strain isolated from a cutaneous infection

Cláudio Tavares Sacchi, Karoline Rodrigues Campos, Bruno Silva Andrade, Verônica Viana Vieira et al.
Frontiers in Microbiology
Diphtheria, Corynebacterium, and Tetanus
article

Virulence and mutations analysis based on the whole genome of a Brazilian Corynebacterium diphtheriae strain isolated from a cutaneous infection

Cláudio Tavares Sacchi, Karoline Rodrigues Campos, Bruno Silva Andrade, Verônica Viana Vieira, Marlon Benedito Nascimento Santos, Diogo Luiz de Carvalho Castro, Marcos Andrade Silva, Max Roberto Batista Araújo, Fernanda Diniz Prates, Hugo Félix Perini, Mireille Ângela Bernardes Sousa, Carlos Henrique Camargo, Louisy Sanches dos Santos, Marcus Vinícius Canário Viana, Juliana Nunes Ramos, Jailan da Silva Sousa, Ana Luíza Mattos‐Guaraldi, Sérgio Bokermann, Lincoln de Oliveira Sant’Anna, Vasco Azevedo, Marcos Vinicius da Silva, Tayná do Carmo Sant’Anna Cardoso
article en

Abstract

<i>Corynebacterium diphtheriae</i> is the main etiological agent of diphtheria, a potentially fatal disease whose most severe signs and symptoms result from the action of an exotoxin, the diphtheria toxin (DT). Although non-toxigenic <i>C. diphtheriae</i> strains have been associated with several diseases, including cutaneous infections and endocarditis, they are not monitored in many countries, and their mechanisms of virulence and antimicrobial resistance remain underexplored. Therefore, this study aimed to provide a comprehensive characterization -through genomic, <i>in vitro</i>, and <i>in vivo</i> analyses - of a non-toxigenic <i>C. diphtheriae</i> strain (46855) isolated from a leg lesion, highlighting its pathogenic potential and resistance profile. The isolate was assigned to a novel sequence type (ST-925) and was found to be resistant to tetracycline and rifampin. Multiple antimicrobial resistance genes were predicted in the genome, such as tet(33), rbpA, and rpoB2, in addition to mutations in the rpoB gene. A diverse set of virulence-associated genes related to adhesion, iron uptake systems, gene regulation, and post-translational modification was also identified. The isolate was able to form biofilm <i>in vitro</i> and exhibited strong virulence in <i>Galleria mellonella</i> larvae and A549 human pneumocyte cells. Finally, the structural analysis of the rpoB gene, carried out for the first time in this study, linked the observed mutations to rifampin resistance in <i>C. diphtheriae</i>. In summary, the data revealed that <i>C. diphtheriae</i> 46855, although non-toxigenic, harbors multiple genes associated with antimicrobial resistance and virulence, emphasizing the need for greater surveillance and functional studies on non-toxigenic strains.

Frontiers in MicrobiologyVol. 16
Universidade Federal de Minas Gerais (BR), Instituto Adolfo Lutz (BR), Southwest Bahia State University (BR), Universidade do Estado do Rio de Janeiro (BR), Universidade Federal do Triângulo Mineiro (BR), Fleury S.A. (Brazil) (BR), Fundação Oswaldo Cruz (BR)
Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Fundação de Amparo à Pesquisa do Estado de Minas Gerais
Openalex Percentile: Top 75%
Diphtheria, Corynebacterium, and Tetanus
DOIOpen Access PDFOpenAlex
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