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Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
Mucosal-adapted bacteriophages as a preventive strategy for a lethal Pseudomonas aeruginosa challenge in mice
Luiz Felipe Leomil Coelho1, Mateus de Souza Terceti1, Sergio Pereira Lima Neto1
1Vaccine Laboratory, Department of Microbiology and Immunology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, Brazil.
Abstract:
Pseudomonas aeruginosa is an emergent threat due to the antimicrobial resistance crisis. Bacteriophages (phages) are promising agents for phage therapy approaches against P. aeruginosa. It has been proposed that metazoans harbor phages on their mucosal surfaces, and this could be exploited for the rational design of prophylactic phage therapy. The goal of this study was to evaluate the potential of phage-mucus interaction to prevent infections caused by P. aeruginosa. We isolated two phages capable of infecting P. aeruginosa. Both are similar in morphology and closely related genetically. However, phage VAC3 is more efficient in replicating in mucin-exposed P. aeruginosa in vitro and is preferentially held in the respiratory tract of C57BL/6 mice. Pre-treatment with VAC3 phage protects mice from a lethal dose of P. aeruginosa while VAC1 does not. This shows that phages adapted to mucosal conditions have potential to be applied as prophylactic measures against an ESKAPE pathogen.
Insights
Phage therapy using Pseudomonas aeruginosa-targeting phages shows promise. Phage VAC3, adapted to mucus, protected mice from infection, suggesting potential for prophylactic phage therapy.
Area of Science:
- Microbiology
- Virology
- Immunology
Background:
- Antimicrobial resistance poses a significant threat, with Pseudomonas aeruginosa as a key pathogen.
- Bacteriophages (phages) are explored as alternatives for phage therapy against P. aeruginosa.
- The presence of phages on mucosal surfaces suggests potential for prophylactic applications.
Purpose of the Study:
- To investigate the interaction between phages and mucus for preventing P. aeruginosa infections.
- To evaluate the efficacy of phages adapted to mucosal conditions for prophylactic phage therapy.
Main Methods:
- Isolation of two P. aeruginosa-infecting phages (VAC3 and VAC1).
- In vitro replication assessment in mucin-exposed P. aeruginosa.
- In vivo respiratory tract retention study in C57BL/6 mice.
- Prophylactic efficacy testing against lethal P. aeruginosa challenge in mice.
Main Results:
- Phage VAC3 demonstrated superior replication in mucin-exposed P. aeruginosa compared to VAC1.
- VAC3 showed preferential retention in the mouse respiratory tract.
- Pre-treatment with VAC3 significantly protected mice from lethal P. aeruginosa infection, unlike VAC1.
Conclusions:
- Phages adapted to mucosal conditions, like VAC3, are effective for prophylactic applications.
- Phage-mucus interaction is a viable strategy for developing preventative phage therapies against P. aeruginosa.
- This study highlights the potential of phages as prophylactic agents against ESKAPE pathogens.
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