Antibiotics | Unique Quinolone Resistance and Zoonotic Potential of Corynebacterium ulcerans from Domestic Animals in Brazil

This study represents the first report in Brazil of non-toxigenic C. ulcerans isolates from domestic animals, revealing a dual GyrA mutation mechanism associated with quinolone resistance. The structural analysis through molecular dynamics simulations provides critical insights for future research on resistance mechanisms and virulence factors.

 

Literature Overview
This article 'Quinolone Resistance and Zoonotic Potential of Corynebacterium ulcerans from Domestic Animals in Brazil', published in the journal Antibiotics, reviews phenotypic and genomic characteristics of non-toxigenic C. ulcerans in Brazilian domestic animals, focusing on quinolone resistance mechanisms and their associations with CRISPR-Cas systems and mobile genetic elements. It emphasizes the importance of monitoring resistance determinants and virulence factors for public health surveillance.

Background Knowledge
Corynebacterium ulcerans is a significant zoonotic pathogen causing diphtheria-like infections, particularly severe in immunocompromised individuals. While tox gene-encoded diphtheria toxin remains a key virulence factor, increasing infections with non-toxigenic strains suggest alternative pathogenic mechanisms. Quinolones (e.g., ciprofloxacin) serve as alternative therapeutic agents, but resistance mechanisms - particularly DNA gyrase (gyrA) mutations - remain poorly characterized. This study employs genomic sequencing, phylogenetic analysis, and structural modeling to investigate resistance mechanisms, combined with CRISPR-Cas and phage analysis to assess genomic plasticity and adaptive capabilities. Bioinformatics predictions identify virulence factors including pilus clusters and iron acquisition systems, providing molecular insights into pathogenic potential and transmission risks for improved surveillance and therapeutic strategies.

 

 

Research Methods and Experiments
This study isolated three non-toxigenic C. ulcerans strains (IHP37393, IHP103889, IHP106492) from Brazilian domestic animals (dogs and cats), identified through MALDI-TOF MS, followed by phenotypic antimicrobial susceptibility testing. Whole-genome sequencing combined with bioinformatics analysis predicted virulence factors, resistance genes, CRISPR-Cas systems, and mobile genetic elements. Molecular dynamics simulations evaluated the structural impact of gyrA mutations on quinolone binding.

Key Conclusions and Perspectives

• All three C. ulcerans isolates belong to sequence type ST-339 with high genomic similarity, yet form two distinct subclones suggesting potential international transmission
• Complete virulence factor repertoire identified including incomplete pilus clusters (spaABC, spaDEF, spaGHI), iron acquisition systems (ciuABCDE, hmuTUV), and PLD gene (pilus-like domain), despite absence of tox gene
• One isolate (IHP37393) demonstrated ciprofloxacin resistance with dual GyrA mutations (S89L and D93G), structural modeling revealed these mutations disrupt magnesium-water bridge interactions, reducing drug binding stability
• CRISPR-Cas system analysis identified conserved type I-E in all strains, with one isolate (IHP106492) additionally harboring type IU, indicating adaptive defense mechanisms
• Phage analysis detected 1-2 intact or questionable prophages per genome, including Rhodococcus phage Jace and Corynebacterium phage Adelaide, potentially associated with antibiotic resistance
• IS element analysis revealed stable genomic presence of IS110, IS21, and IS256 families, suggesting contributions to genomic plasticity

Research Significance and Prospects
This study reports the first quinolone resistance mechanism in Brazilian C. ulcerans isolates, providing critical baseline data for clinical management and public health monitoring. Future global genomic surveillance should assess resistance dissemination patterns and host adaptation dynamics. The molecular modeling approach presented here offers structural frameworks for developing novel quinolone derivatives and optimizing antimicrobial therapies.

 

 

Conclusion
This study characterizes genomic features of non-toxigenic C. ulcerans from Brazilian domestic animals, highlighting quinolone resistance through dual GyrA mutations (S89L and D93G) and associated structural alterations. The presence of multiple virulence factors and CRISPR-Cas systems indicates genomic plasticity and host adaptation capacity. These findings underscore the necessity for continuous antimicrobial resistance monitoring of zoonotic pathogens, while providing reference genomic data for future mechanistic studies. Although tox gene-negative, the identified virulence elements (pilus structures, iron acquisition systems) confirm pathogenic potential warranting public health attention.

 

Fernanda Diniz Prates, Max Roberto Batista Araújo, Jailan da Silva Sousa, Louisy Sanches dos Santos, and Vasco Ariston de Carvalho Azevedo. Quinolone Resistance and Zoonotic Potential of Corynebacterium ulcerans from Domestic Animals in Brazil. Antibiotics.