Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis
The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing , a pathogen commonly found in patients with atopic dermatitis (AD) and an important facto...
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| Published in | Science translational medicine Vol. 9; no. 378 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
22.02.2017
|
| Subjects | |
| Online Access | Get more information |
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| Abstract | The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing
, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against
was performed on isolates of coagulase-negative
(CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by
The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including
and
These AMPs were strain-specific, highly potent, selectively killed
, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by
These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease. |
|---|---|
| AbstractList | The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing
, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against
was performed on isolates of coagulase-negative
(CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by
The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including
and
These AMPs were strain-specific, highly potent, selectively killed
, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by
These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease. |
| Author | Zengler, Karsten Kotol, Paul F Shafiq, Faiza David, Gloria Chun, Kimberly A Bouslimani, Amina Narala, Saisindhu Leung, Donald Y M Hata, Tissa R Streib, Joanne Chen, Tiffany H Artis, Keli Taylor, Patricia Kim, Ji-Nu Gill, Steven R Dorrestein, Pieter C Lockhart, Alexandre Latif, Haythem Nakatsuji, Teruaki Melnik, Alexey V Two, Aimee M Grier, Alex Yun, Tong Gallo, Richard L |
| Author_xml | – sequence: 1 givenname: Teruaki orcidid: 0000-0002-6187-2991 surname: Nakatsuji fullname: Nakatsuji, Teruaki organization: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 2 givenname: Tiffany H surname: Chen fullname: Chen, Tiffany H organization: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 3 givenname: Saisindhu orcidid: 0000-0001-9913-951X surname: Narala fullname: Narala, Saisindhu organization: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 4 givenname: Kimberly A surname: Chun fullname: Chun, Kimberly A organization: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 5 givenname: Aimee M surname: Two fullname: Two, Aimee M organization: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 6 givenname: Tong orcidid: 0000-0003-2003-1843 surname: Yun fullname: Yun, Tong organization: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 7 givenname: Faiza orcidid: 0000-0001-6211-7712 surname: Shafiq fullname: Shafiq, Faiza organization: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 8 givenname: Paul F surname: Kotol fullname: Kotol, Paul F organization: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 9 givenname: Amina orcidid: 0000-0002-1635-532X surname: Bouslimani fullname: Bouslimani, Amina organization: Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 10 givenname: Alexey V surname: Melnik fullname: Melnik, Alexey V organization: Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 11 givenname: Haythem orcidid: 0000-0001-5738-2802 surname: Latif fullname: Latif, Haythem organization: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 12 givenname: Ji-Nu surname: Kim fullname: Kim, Ji-Nu organization: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 13 givenname: Alexandre surname: Lockhart fullname: Lockhart, Alexandre organization: Rho Federal Systems Division Inc., Chapel Hill, NC 27517, USA – sequence: 14 givenname: Keli orcidid: 0000-0002-7158-6382 surname: Artis fullname: Artis, Keli organization: Rho Federal Systems Division Inc., Chapel Hill, NC 27517, USA – sequence: 15 givenname: Gloria surname: David fullname: David, Gloria organization: Rho Federal Systems Division Inc., Chapel Hill, NC 27517, USA – sequence: 16 givenname: Patricia surname: Taylor fullname: Taylor, Patricia organization: Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA – sequence: 17 givenname: Joanne orcidid: 0000-0002-9780-3437 surname: Streib fullname: Streib, Joanne organization: Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA – sequence: 18 givenname: Pieter C orcidid: 0000-0002-3003-1030 surname: Dorrestein fullname: Dorrestein, Pieter C organization: Departments of Chemistry, Biochemistry and Pharmacology, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 19 givenname: Alex surname: Grier fullname: Grier, Alex organization: Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14611, USA – sequence: 20 givenname: Steven R orcidid: 0000-0002-2408-1373 surname: Gill fullname: Gill, Steven R organization: Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14611, USA – sequence: 21 givenname: Karsten surname: Zengler fullname: Zengler, Karsten organization: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 22 givenname: Tissa R surname: Hata fullname: Hata, Tissa R organization: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA – sequence: 23 givenname: Donald Y M surname: Leung fullname: Leung, Donald Y M organization: Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA – sequence: 24 givenname: Richard L orcidid: 0000-0002-1401-7861 surname: Gallo fullname: Gallo, Richard L email: rgallo@ucsd.edu organization: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA. rgallo@ucsd.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28228596$$D View this record in MEDLINE/PubMed |
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| Snippet | The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on... |
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| SubjectTerms | Amino Acid Sequence Animals Anti-Infective Agents - pharmacology Anti-Infective Agents - therapeutic use Antimicrobial Cationic Peptides - chemistry Antimicrobial Cationic Peptides - pharmacology Bacteria - drug effects Coagulase - metabolism Colony Count, Microbial Dermatitis, Atopic - drug therapy Dermatitis, Atopic - microbiology Dysbiosis - drug therapy Dysbiosis - microbiology Humans Mice Microbiota - drug effects Skin - microbiology Staphylococcus aureus - drug effects Staphylococcus aureus - growth & development Sus scrofa |
| Title | Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis |
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