The effectiveness of bacteriophages against methicillin-resistant Staphylococcus aureus ST398 nasal colonization in pigs

Koen M. Verstappen, Pawel Tulinski, Birgitta Duim, Ad C. Fluit, Jennifer Carney, Arie Van Nes, Jaap A. Wagenaar

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Abstract

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.

Original languageEnglish
Article numbere0160242
JournalPLoS ONE
Volume11
Issue number8
DOIs
Publication statusPublished - 2016

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Bacteriophages
Methicillin
Methicillin-Resistant Staphylococcus aureus
Nose
bacteriophages
Swine
swine
piglets
methicillin-resistant Staphylococcus aureus
Animals
Mupirocin
occupational exposure
nasal mucosa
Nasal Mucosa
Pathogens
Occupational Exposure
in vivo studies
antibiotic resistance
animals
explants

Cite this

Verstappen, K. M., Tulinski, P., Duim, B., Fluit, A. C., Carney, J., Van Nes, A., & Wagenaar, J. A. (2016). The effectiveness of bacteriophages against methicillin-resistant Staphylococcus aureus ST398 nasal colonization in pigs. PLoS ONE, 11(8), [e0160242]. https://doi.org/10.1371/journal.pone.0160242
Verstappen, Koen M. ; Tulinski, Pawel ; Duim, Birgitta ; Fluit, Ad C. ; Carney, Jennifer ; Van Nes, Arie ; Wagenaar, Jaap A. / The effectiveness of bacteriophages against methicillin-resistant Staphylococcus aureus ST398 nasal colonization in pigs. In: PLoS ONE. 2016 ; Vol. 11, No. 8.
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abstract = "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.",
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Verstappen, KM, Tulinski, P, Duim, B, Fluit, AC, Carney, J, Van Nes, A & Wagenaar, JA 2016, 'The effectiveness of bacteriophages against methicillin-resistant Staphylococcus aureus ST398 nasal colonization in pigs', PLoS ONE, vol. 11, no. 8, e0160242. https://doi.org/10.1371/journal.pone.0160242

The effectiveness of bacteriophages against methicillin-resistant Staphylococcus aureus ST398 nasal colonization in pigs. / Verstappen, Koen M.; Tulinski, Pawel; Duim, Birgitta; Fluit, Ad C.; Carney, Jennifer; Van Nes, Arie; Wagenaar, Jaap A.

In: PLoS ONE, Vol. 11, No. 8, e0160242, 2016.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - The effectiveness of bacteriophages against methicillin-resistant Staphylococcus aureus ST398 nasal colonization in pigs

AU - Verstappen, Koen M.

AU - Tulinski, Pawel

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AU - Carney, Jennifer

AU - Van Nes, Arie

AU - Wagenaar, Jaap A.

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AB - 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.

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