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Updated: Nov 30, 2025
Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Multidrug-Resistant Proteus mirabilis Strain with Cointegrate Plasmid
Andrey Shelenkov1, Lyudmila Petrova2, Valeria Fomina2
1Central Research Institute of Epidemiology, Novogireevskaya str. 3a, 111123 Moscow, Russia.
Abstract:
Proteus mirabilis is a component of the normal intestinal microflora of humans and animals, but can cause urinary tract infections and even sepsis in hospital settings. In recent years, the number of multidrug-resistant P. mirabilis isolates, including the ones producing extended-spectrum β-lactamases (ESBLs), is increasing worldwide. However, the number of investigations dedicated to this species, especially, whole-genome sequencing, is much lower in comparison to the members of the ESKAPE pathogens group. This study presents a detailed analysis of clinical multidrug-resistant ESBL-producing P. mirabilis isolate using short- and long-read whole-genome sequencing, which allowed us to reveal possible horizontal gene transfer between Klebsiella pneumoniae and P. mirabilis plasmids and to locate the CRISPR-Cas system in the genome together with its probable phage targets, as well as multiple virulence genes. We believe that the data presented will contribute to the understanding of antibiotic resistance acquisition and virulence mechanisms for this important pathogen.
Insights
Multidrug-resistant Proteus mirabilis, a cause of hospital infections, is increasingly studied. Whole-genome sequencing revealed its antibiotic resistance mechanisms and virulence factors, including potential gene transfer from Klebsiella pneumoniae.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Proteus mirabilis is a common gut bacterium that can cause severe hospital-acquired infections.
- The prevalence of multidrug-resistant P. mirabilis, particularly those producing extended-spectrum beta-lactamases (ESBLs), is rising globally.
- Research on P. mirabilis, especially whole-genome sequencing, lags behind other major pathogens.
Purpose of the Study:
- To conduct a comprehensive genomic analysis of a multidrug-resistant, ESBL-producing P. mirabilis clinical isolate.
- To investigate mechanisms of antibiotic resistance and virulence in P. mirabilis.
- To compare P. mirabilis genomics with other ESKAPE pathogens.
Main Methods:
- Utilized both short-read and long-read whole-genome sequencing technologies.
- Performed detailed genomic analysis to identify resistance genes, virulence factors, and mobile genetic elements.
- Investigated the CRISPR-Cas system and potential phage targets within the P. mirabilis genome.
Main Results:
- Identified horizontal gene transfer events, suggesting plasmid exchange between P. mirabilis and Klebsiella pneumoniae.
- Located a CRISPR-Cas system and its putative phage targets, offering insights into phage resistance.
- Characterized multiple virulence genes contributing to P. mirabilis pathogenicity.
- Confirmed the presence of ESBL genes conferring multidrug resistance.
Conclusions:
- Genomic insights into P. mirabilis provide a foundation for understanding its increasing resistance and virulence.
- The study highlights potential inter-species gene transfer as a mechanism for resistance acquisition.
- Further research on P. mirabilis is crucial for developing effective treatments against this emerging pathogen.
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