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The Effectiveness of Bacteriophages against Methicillin-Resistant Staphylococcus aureus ST398 Nasal Colonization in
Koen M Verstappen1, Pawel Tulinski1, Birgitta Duim1
1Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Unlabelled:
Methicillin-resistant Staphylococcus aureus (MRSA) is an important colonizer in animals and an opportunistic pathogen in humans. In humans, MRSA can cause infections that might be difficult to treat because of antimicrobial resistance. The use of bacteriophages has been suggested as a potential approach for the control of MRSA colonization to minimize the-often occupational-exposure of humans. The aim of this study was to assess the efficacy of bacteriophage treatment on porcine nasal colonization with MRSA in vitro, in vivo, and ex vivo. The effectiveness of a bacteriophage combination of phage K*710 and P68 was assessed in vitro by incubating them with MRSA V0608892/1 (ST398) measuring the OD600 hourly. To study the in vivo effect, bacteriophages were administered in a gel developed for human application, which contain 109 plaque-forming units (pfu)/mL (K and P68 in a 19.25:1 ratio) for 5 days to piglets (N = 8) that were experimentally colonized with the MRSA strain. Eight piglets experimentally colonized were used as a negative control. The MRSA strain was also used to colonize porcine nasal mucosa explants and bacteriophages were applied to assess the ex vivo efficacy of treatment. Bacteriophages were effective in vitro. In vivo, sixteen piglets were colonized with MRSA but the number of CFU recovered after the application of the bacteriophages in 8 piglets was not reduced compared to the control animals (approx. 105 CFU/swab). In the ex vivo model, 108 CFU were used to establish colonization with MRSA; a reduction of colonization was not observed after application of bacteriophages. However, application of mupirocin both in vivo and ex vivo resulted in a near eradication of MRSA.
In Conclusion:
i) The MRSA strain was killed in the presence of the bacteriophages phage K*710 and P68 in vitro. ii) Bacteriophages did not reduce porcine nasal colonization in vivo or ex vivo. Physiological in vivo and ex vivo conditions may explain these observations. Efficacy in the ex vivo model matched that of the in vivo system.
Insights
Bacteriophages effectively killed methicillin-resistant Staphylococcus aureus (MRSA) in lab tests but failed to reduce MRSA nasal colonization in pigs, both in live animals and tissue samples. Mupirocin, however, nearly eradicated MRSA in both settings.
Area of Science:
- Veterinary Microbiology
- Antimicrobial Resistance
- Bacteriophage Therapy
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat due to its animal reservoir and potential for human infection, often complicated by antibiotic resistance.
- Bacteriophage therapy is explored as a strategy to control MRSA colonization and reduce human exposure, particularly occupational risks.
Purpose of the Study:
- To evaluate the efficacy of a specific bacteriophage combination (phage K*710 and P68) against porcine nasal colonization by MRSA.
- To assess bacteriophage effectiveness in vitro, in vivo (in piglets), and ex vivo (using nasal mucosa explants).
Main Methods:
- In vitro: Bacteriophages were incubated with MRSA, monitoring optical density.
- In vivo: Piglets colonized with MRSA received bacteriophages in a gel formulation for five days; a control group received no treatment.
- Ex vivo: Porcine nasal mucosa explants colonized with MRSA were treated with bacteriophages.
Main Results:
- Bacteriophages demonstrated effectiveness in killing MRSA in vitro.
- In vivo, bacteriophage treatment did not significantly reduce MRSA nasal colonization in piglets compared to controls.
- Ex vivo, bacteriophages failed to reduce MRSA colonization on nasal mucosa explants.
- Mupirocin treatment resulted in near-complete MRSA eradication in both in vivo and ex vivo models.
Conclusions:
- The bacteriophage combination of K*710 and P68 was effective against MRSA in vitro.
- Bacteriophages did not effectively reduce MRSA nasal colonization in pigs under in vivo or ex vivo conditions.
- Physiological differences in in vivo and ex vivo environments may account for the lack of efficacy, with ex vivo results mirroring in vivo findings.
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