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Isolation and Characterization of the Acadevirus Members BigMira and MidiMira Infecting a Highly Pathogenic Proteus
Jéssica Duarte da Silva1, Lene Bens2, Adriele J do Carmo Santos1
1Laboratory of Molecular Immunovirology, Department of Microbiology, Federal University of Viçosa, Viçosa 36570-900, MG, Brazil.
Abstract:
Proteus mirabilis is an opportunistic pathogen and is responsible for more than 40% of all cases of catheter-associated urinary tract infections (CAUTIs). Healthcare-associated infections have been aggravated by the constant emergence of antibiotic-resistant bacterial strains. Because of this, the use of phages to combat bacterial infections gained renewed interest. In this study, we describe the biological and genomic features of two P. mirabilis phages, named BigMira and MidiMira. These phages belong to the Acadevirus genus (family Autographiviridae). BigMira and MidiMira are highly similar, differing only in four missense mutations in their phage tail fiber. These mutations are sufficient to impact the phages' depolymerase activity. Subsequently, the comparative genomic analysis of ten clinical P. mirabilis strains revealed differences in their antibiotic resistance profiles and lipopolysaccharide locus, with the latter potentially explaining the host range data of the phages. The massive presence of antimicrobial resistance genes, especially in the phages' isolation strain P. mirabilis MCS, highlights the challenges in treating infections caused by multidrug-resistant bacteria. The findings reinforce BigMira and MidiMira phages as candidates for phage therapy purposes.
Insights
Two novel phages, BigMira and MidiMira, show potential for treating Proteus mirabilis infections, including challenging multidrug-resistant strains. These phages offer a promising alternative to antibiotics for catheter-associated urinary tract infections (CAUTIs).
Area of Science:
- Microbiology
- Bacteriology
- Virology
Background:
- Proteus mirabilis is a major cause of catheter-associated urinary tract infections (CAUTIs), exacerbated by antibiotic resistance.
- Bacteriophage therapy is regaining interest as a strategy against multidrug-resistant bacterial pathogens.
Purpose of the Study:
- To characterize the biological and genomic features of two novel P. mirabilis phages, BigMira and MidiMira.
- To analyze the genomic diversity of clinical P. mirabilis strains and correlate it with phage host range.
Main Methods:
- Isolation and characterization of BigMira and MidiMira phages.
- Comparative genomic analysis of P. mirabilis strains.
- Assessment of phage depolymerase activity and host range.
Main Results:
- BigMira and MidiMira are Acadevirus phages highly similar to each other, with minor tail fiber mutations affecting depolymerase activity.
- Clinical P. mirabilis strains exhibit varied antibiotic resistance and lipopolysaccharide locus profiles, influencing phage host range.
- The P. mirabilis isolation strain harbors numerous antimicrobial resistance genes, underscoring treatment challenges.
Conclusions:
- BigMira and MidiMira phages demonstrate potential as therapeutic agents against P. mirabilis infections.
- Genomic variations in P. mirabilis impact susceptibility to phage therapy.
- Phage therapy presents a viable option for combating multidrug-resistant P. mirabilis infections.
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