Harnessing diversity and antagonism within the pig skin microbiota to identify novel mediators of colonization resistance to methicillin-resistant Staphylococcus aureus
ABSTRACT The microbiota mediate multiple aspects of skin barrier function, including colonization resistance to pathogens such as Staphylococcus aureus. The endogenous skin microbiota limits S. aureus colonization via competition and direct inhibition. Novel mechanisms of colonization resistance are...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-08-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00177-23 |
| _version_ | 1827855262216617984 |
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| author | Monica Wei Laurice Flowers Simon A. B. Knight Qi Zheng Sofia Murga-Garrido Aayushi Uberoi Jamie Ting-Chun Pan Jasmine Walsh Erin Schroeder Emily W. Chu Amy Campbell Daniel Shin Charles W. Bradley Raimon Duran-Struuck Elizabeth A. Grice |
| author_facet | Monica Wei Laurice Flowers Simon A. B. Knight Qi Zheng Sofia Murga-Garrido Aayushi Uberoi Jamie Ting-Chun Pan Jasmine Walsh Erin Schroeder Emily W. Chu Amy Campbell Daniel Shin Charles W. Bradley Raimon Duran-Struuck Elizabeth A. Grice |
| author_sort | Monica Wei |
| collection | DOAJ |
| description | ABSTRACT The microbiota mediate multiple aspects of skin barrier function, including colonization resistance to pathogens such as Staphylococcus aureus. The endogenous skin microbiota limits S. aureus colonization via competition and direct inhibition. Novel mechanisms of colonization resistance are promising therapeutic targets for drug-resistant infections, such as those caused by methicillin-resistant S. aureus (MRSA). Here, we developed and characterized a swine model of topical microbiome perturbation and MRSA colonization. As in other model systems, topical antimicrobial treatment had a little discernable effect on community diversity though the overall microbial load was sensitive to multiple types of intervention, including swabbing. In parallel, we established a porcine skin culture collection and screened 7,700 isolates for MRSA inhibition. Using genomic and phenotypic criteria, we curated three isolates to investigate whether prophylactic colonization would inhibit MRSA colonization in vivo. The three-member consortium together, but not individually, provided protection against MRSA colonization, suggesting cooperation and/or synergy among the strains. Inhibitory isolates were represented across all major phyla of the pig skin microbiota and did not have a strong preference for inhibiting closely related species, suggesting that relatedness is not a condition of antagonism. These findings reveal the porcine skin as an underexplored reservoir of skin commensal species with the potential to prevent MRSA colonization and infection. IMPORTANCE The skin microbiota is protective against pathogens or opportunists such as S. aureus, the most common cause of skin and soft tissue infections. S. aureus can colonize normal skin and nasal passages, and colonization is a risk factor for infection, especially on breach of the skin barrier. Here, we established a pig model to study the competitive mechanisms of the skin microbiota and their role in preventing colonization by MRSA. This drug-resistant strain is also a livestock pathogen, and swine herds can be reservoirs of MRSA carriage. From 7,700 cultured skin isolates, we identified 37 unique species across three phyla that inhibited MRSA. A synthetic community of three inhibitory isolates provided protection together, but not individually, in vivo in a murine model of MRSA colonization. These findings suggest that antagonism is widespread in the pig skin microbiota, and these competitive interactions may be exploited to prevent MRSA colonization. |
| first_indexed | 2024-03-12T11:42:33Z |
| format | Article |
| id | doaj.art-686198a86f14431a9493458327c5a513 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-03-12T11:42:33Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-686198a86f14431a9493458327c5a5132023-08-31T14:26:41ZengAmerican Society for MicrobiologymSphere2379-50422023-08-018410.1128/msphere.00177-23Harnessing diversity and antagonism within the pig skin microbiota to identify novel mediators of colonization resistance to methicillin-resistant Staphylococcus aureusMonica Wei0Laurice Flowers1Simon A. B. Knight2Qi Zheng3Sofia Murga-Garrido4Aayushi Uberoi5Jamie Ting-Chun Pan6Jasmine Walsh7Erin Schroeder8Emily W. Chu9Amy Campbell10Daniel Shin11Charles W. Bradley12Raimon Duran-Struuck13Elizabeth A. Grice14Department of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USADepartment of Dermatology & Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USAABSTRACT The microbiota mediate multiple aspects of skin barrier function, including colonization resistance to pathogens such as Staphylococcus aureus. The endogenous skin microbiota limits S. aureus colonization via competition and direct inhibition. Novel mechanisms of colonization resistance are promising therapeutic targets for drug-resistant infections, such as those caused by methicillin-resistant S. aureus (MRSA). Here, we developed and characterized a swine model of topical microbiome perturbation and MRSA colonization. As in other model systems, topical antimicrobial treatment had a little discernable effect on community diversity though the overall microbial load was sensitive to multiple types of intervention, including swabbing. In parallel, we established a porcine skin culture collection and screened 7,700 isolates for MRSA inhibition. Using genomic and phenotypic criteria, we curated three isolates to investigate whether prophylactic colonization would inhibit MRSA colonization in vivo. The three-member consortium together, but not individually, provided protection against MRSA colonization, suggesting cooperation and/or synergy among the strains. Inhibitory isolates were represented across all major phyla of the pig skin microbiota and did not have a strong preference for inhibiting closely related species, suggesting that relatedness is not a condition of antagonism. These findings reveal the porcine skin as an underexplored reservoir of skin commensal species with the potential to prevent MRSA colonization and infection. IMPORTANCE The skin microbiota is protective against pathogens or opportunists such as S. aureus, the most common cause of skin and soft tissue infections. S. aureus can colonize normal skin and nasal passages, and colonization is a risk factor for infection, especially on breach of the skin barrier. Here, we established a pig model to study the competitive mechanisms of the skin microbiota and their role in preventing colonization by MRSA. This drug-resistant strain is also a livestock pathogen, and swine herds can be reservoirs of MRSA carriage. From 7,700 cultured skin isolates, we identified 37 unique species across three phyla that inhibited MRSA. A synthetic community of three inhibitory isolates provided protection together, but not individually, in vivo in a murine model of MRSA colonization. These findings suggest that antagonism is widespread in the pig skin microbiota, and these competitive interactions may be exploited to prevent MRSA colonization.https://journals.asm.org/doi/10.1128/msphere.00177-23skinskin microbiomemicrobe–microbe interactionsStaphylococcus aureusporcine skincolonization resistance |
| spellingShingle | Monica Wei Laurice Flowers Simon A. B. Knight Qi Zheng Sofia Murga-Garrido Aayushi Uberoi Jamie Ting-Chun Pan Jasmine Walsh Erin Schroeder Emily W. Chu Amy Campbell Daniel Shin Charles W. Bradley Raimon Duran-Struuck Elizabeth A. Grice Harnessing diversity and antagonism within the pig skin microbiota to identify novel mediators of colonization resistance to methicillin-resistant Staphylococcus aureus mSphere skin skin microbiome microbe–microbe interactions Staphylococcus aureus porcine skin colonization resistance |
| title | Harnessing diversity and antagonism within the pig skin microbiota to identify novel mediators of colonization resistance to methicillin-resistant Staphylococcus aureus |
| title_full | Harnessing diversity and antagonism within the pig skin microbiota to identify novel mediators of colonization resistance to methicillin-resistant Staphylococcus aureus |
| title_fullStr | Harnessing diversity and antagonism within the pig skin microbiota to identify novel mediators of colonization resistance to methicillin-resistant Staphylococcus aureus |
| title_full_unstemmed | Harnessing diversity and antagonism within the pig skin microbiota to identify novel mediators of colonization resistance to methicillin-resistant Staphylococcus aureus |
| title_short | Harnessing diversity and antagonism within the pig skin microbiota to identify novel mediators of colonization resistance to methicillin-resistant Staphylococcus aureus |
| title_sort | harnessing diversity and antagonism within the pig skin microbiota to identify novel mediators of colonization resistance to methicillin resistant staphylococcus aureus |
| topic | skin skin microbiome microbe–microbe interactions Staphylococcus aureus porcine skin colonization resistance |
| url | https://journals.asm.org/doi/10.1128/msphere.00177-23 |
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