Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius
Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We scree...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/66793 |
| _version_ | 1797998451265372160 |
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| author | Alan M O'Neill Kate A Worthing Nikhil Kulkarni Fengwu Li Teruaki Nakatsuji Dominic McGrosso Robert H Mills Gayathri Kalla Joyce Y Cheng Jacqueline M Norris Kit Pogliano Joe Pogliano David J Gonzalez Richard L Gallo |
| author_facet | Alan M O'Neill Kate A Worthing Nikhil Kulkarni Fengwu Li Teruaki Nakatsuji Dominic McGrosso Robert H Mills Gayathri Kalla Joyce Y Cheng Jacqueline M Norris Kit Pogliano Joe Pogliano David J Gonzalez Richard L Gallo |
| author_sort | Alan M O'Neill |
| collection | DOAJ |
| description | Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We screened a collection of diverse staphylococcus species from domestic dogs and cats for antimicrobial activity against MRSP. A unique strain (S. felis C4) was isolated from feline skin that inhibited MRSP and multiple gram-positive pathogens. Whole genome sequencing and mass spectrometry revealed several secreted antimicrobials including a thiopeptide bacteriocin micrococcin P1 and phenol-soluble modulin beta (PSMβ) peptides that exhibited antimicrobial and anti-inflammatory activity. Fluorescence and electron microscopy revealed that S. felis antimicrobials inhibited translation and disrupted bacterial but not eukaryotic cell membranes. Competition experiments in mice showed that S. felis significantly reduced MRSP skin colonization and an antimicrobial extract from S. felis significantly reduced necrotic skin injury from MRSP infection. These findings indicate a feline commensal bacterium that could be utilized in bacteriotherapy against difficult-to-treat animal and human skin infections. |
| first_indexed | 2024-04-11T10:48:58Z |
| format | Article |
| id | doaj.art-8239653fab1c46dc8610832c2aa22e68 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:48:58Z |
| publishDate | 2021-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8239653fab1c46dc8610832c2aa22e682022-12-22T04:28:58ZengeLife Sciences Publications LtdeLife2050-084X2021-10-011010.7554/eLife.66793Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermediusAlan M O'Neill0https://orcid.org/0000-0002-5892-6477Kate A Worthing1https://orcid.org/0000-0001-8713-7189Nikhil Kulkarni2Fengwu Li3Teruaki Nakatsuji4Dominic McGrosso5Robert H Mills6Gayathri Kalla7Joyce Y Cheng8Jacqueline M Norris9Kit Pogliano10https://orcid.org/0000-0002-7868-3345Joe Pogliano11David J Gonzalez12Richard L Gallo13https://orcid.org/0000-0002-1401-7861Department of Dermatology, University of California, San Diego, San Diego, United StatesCollege of Veterinary Medicine, University of Arizona, Oro Valley, United StatesDepartment of Dermatology, University of California, San Diego, San Diego, United StatesDepartment of Dermatology, University of California, San Diego, San Diego, United StatesDepartment of Dermatology, University of California, San Diego, San Diego, United StatesDepartment of Pharmacology, University of California, San Diego, San Diego, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, United StatesDepartment of Pharmacology, University of California, San Diego, San Diego, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, United StatesDivision of Biological Sciences, University of California, San Diego, San Diego, United StatesDepartment of Dermatology, University of California, San Diego, San Diego, United StatesSydney School of Veterinary Science, University of Sydney, Sydney, AustraliaDivision of Biological Sciences, University of California, San Diego, San Diego, United StatesDivision of Biological Sciences, University of California, San Diego, San Diego, United StatesDepartment of Pharmacology, University of California, San Diego, San Diego, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, United StatesDepartment of Dermatology, University of California, San Diego, San Diego, United StatesMethicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We screened a collection of diverse staphylococcus species from domestic dogs and cats for antimicrobial activity against MRSP. A unique strain (S. felis C4) was isolated from feline skin that inhibited MRSP and multiple gram-positive pathogens. Whole genome sequencing and mass spectrometry revealed several secreted antimicrobials including a thiopeptide bacteriocin micrococcin P1 and phenol-soluble modulin beta (PSMβ) peptides that exhibited antimicrobial and anti-inflammatory activity. Fluorescence and electron microscopy revealed that S. felis antimicrobials inhibited translation and disrupted bacterial but not eukaryotic cell membranes. Competition experiments in mice showed that S. felis significantly reduced MRSP skin colonization and an antimicrobial extract from S. felis significantly reduced necrotic skin injury from MRSP infection. These findings indicate a feline commensal bacterium that could be utilized in bacteriotherapy against difficult-to-treat animal and human skin infections.https://elifesciences.org/articles/66793staphylococcus felisStaphylococcus aureusstaphylococcus pseudintermediusskininfectionantimicrobial |
| spellingShingle | Alan M O'Neill Kate A Worthing Nikhil Kulkarni Fengwu Li Teruaki Nakatsuji Dominic McGrosso Robert H Mills Gayathri Kalla Joyce Y Cheng Jacqueline M Norris Kit Pogliano Joe Pogliano David J Gonzalez Richard L Gallo Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius eLife staphylococcus felis Staphylococcus aureus staphylococcus pseudintermedius skin infection antimicrobial |
| title | Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius |
| title_full | Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius |
| title_fullStr | Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius |
| title_full_unstemmed | Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius |
| title_short | Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius |
| title_sort | antimicrobials from a feline commensal bacterium inhibit skin infection by drug resistant s pseudintermedius |
| topic | staphylococcus felis Staphylococcus aureus staphylococcus pseudintermedius skin infection antimicrobial |
| url | https://elifesciences.org/articles/66793 |
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