title: Antimicrobials from human skin commensal bacteria protect againstStaphylococcus aureusand are deficient in atopic dermatitis.
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 killingStaphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity againstS. aureuswas performed on isolates of coagulase-negativeStaphylococcus(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 byS. aureusThe antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species includingStaphylococcus epidermidisandStaphylococcus hominisThese AMPs were strain-specific, highly potent, selectively killedS. aureus, 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 byS. aureusThese findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Teruaki
authors.identifier: 0000-0002-6187-2991
authors.initials: T
authors.lastname: Nakatsuji
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Tiffany H
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Saisindhu
authors.identifier: 0000-0001-9913-951X
authors.initials: S
authors.lastname: Narala
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Chun
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Two
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Tong
authors.identifier: 0000-0003-2003-1843
authors.initials: T
authors.lastname: Yun
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Faiza
authors.identifier: 0000-0001-6211-7712
authors.initials: F
authors.lastname: Shafiq
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Kotol
authors.affiliation: Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Amina
authors.identifier: 0000-0002-1635-532X
authors.initials: A
authors.lastname: Bouslimani
authors.affiliation: Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Melnik
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Haythem
authors.identifier: 0000-0001-5738-2802
authors.initials: H
authors.lastname: Latif
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Ji-Nu
authors.initials: JN
authors.lastname: Kim
authors.affiliation: Rho Federal Systems Division Inc., Chapel Hill, NC 27517, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lockhart
authors.affiliation: Rho Federal Systems Division Inc., Chapel Hill, NC 27517, USA.
authors.forename: Keli
authors.identifier: 0000-0002-7158-6382
authors.initials: K
authors.lastname: Artis
authors.affiliation: Rho Federal Systems Division Inc., Chapel Hill, NC 27517, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: David
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Taylor
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Joanne
authors.identifier: 0000-0002-9780-3437
authors.initials: J
authors.lastname: Streib
authors.affiliation: Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92092, USA.|Departments of Chemistry, Biochemistry and Pharmacology, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Pieter C
authors.identifier: 0000-0002-3003-1030
authors.initials: PC
authors.lastname: Dorrestein
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14611, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Grier
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14611, USA.
authors.forename: Steven R
authors.identifier: 0000-0002-2408-1373
authors.initials: SR
authors.lastname: Gill
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Karsten
authors.initials: K
authors.lastname: Zengler
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA.
authors.forename: Tissa R
authors.initials: TR
authors.lastname: Hata
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
authors.affiliation: Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA. rgallo@ucsd.edu.
authors.forename: Richard L
authors.identifier: 0000-0002-1401-7861
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D003030:Coagulase / Q000378:metabolism; D015169:Colony Count, Microbial; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000382:microbiology*; D064806:Dysbiosis / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D051379:Mice; D064307:Microbiota / Q000187:drug effects; D012867:Skin / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D034421:Sus scrofa
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D003030:Coagulase