A Cutibacterium acnes antibiotic modulates human skin microbiota composition in hair follicles

被引:105
作者
Claesen, Jan [1 ]
Spagnolo, Jennifer B. [2 ,3 ]
Ramos, Stephany Flores [2 ]
Kurita, Kenji L. [4 ,21 ]
Byrd, Allyson L. [5 ,22 ]
Aksenov, Alexander A. [6 ,7 ]
Melnik, Alexey, V [6 ,7 ]
Wong, Weng R. [8 ]
Wang, Shuo [9 ]
Hernandez, Ryan D. [8 ,10 ,11 ]
Donia, Mohamed S. [12 ]
Dorrestein, Pieter C. [6 ,7 ]
Kong, Heidi H. [13 ]
Segre, Julia A. [5 ]
Linington, Roger G. [4 ]
Fischbach, Michael A. [14 ,15 ]
Lemon, Katherine P. [2 ,16 ,17 ,18 ,19 ,20 ]
机构
[1] Cleveland Clin, Dept Cardiovasc & Metab Sci, Lerner Res Inst, Cleveland, OH 44195 USA
[2] Forsyth Inst, Microbiol, Cambridge, MA 02142 USA
[3] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA
[4] Simon Fraser Univ, Dept Chem, Burnaby, BC V5A 1S6, Canada
[5] NHGRI, Microbial Genom Sect, NIH, Bethesda, MD 20892 USA
[6] Univ Calif San Diego, Collaborat Mass Spectrometry Innovat Ctr, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
[7] Univ Calif San Diego, Ctr Microbiome Innovat, La Jolla, CA 92093 USA
[8] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA
[9] Princeton Univ, Dept Chem & Biol Engn, Princeton, NJ 08540 USA
[10] McGill Univ, Dept Human Genet, Montreal, PQ H3A 0C7, Canada
[11] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0C7, Canada
[12] Princeton Univ, Dept Mol Biol, Princeton, NJ 08540 USA
[13] NIAMSD, Dermatol Branch, NIH, Bethesda, MD 20892 USA
[14] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA
[15] Stanford Univ, ChEM H, Stanford, CA 94305 USA
[16] Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
[17] Harvard Med Sch, Boston, MA 02115 USA
[18] Baylor Coll Med, Alkek Ctr Metagen & Microbiome Res, Dept Mol Virol & Microbiol, Houston, TX 77030 USA
[19] Texas Childrens Hosp, Dept Pediat, Sect Infect Dis, Houston, TX 77030 USA
[20] Baylor Coll Med, Houston, TX 77030 USA
[21] Genentech Inc, Small Mol Pharmaceut Sci, San Francisco, CA 94080 USA
[22] Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 USA
基金
加拿大自然科学与工程研究理事会;
关键词
PROPIONIBACTERIUM-ACNES; CLOSTRIDIUM-DIFFICILE; ASSOCIATION; LFF571;
D O I
10.1126/scitranslmed.aay5445
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The composition of the skin microbiota varies widely among individuals when sampled at the same body site. A key question is which molecular factors determine strain-level variability within sub-ecosystems of the skin microbiota. Here, we used a genomics-guided approach to identify an antibacterial biosynthetic gene cluster in Cutibacterium acnes (formerly Propionibacterium acnes), a human skin commensal bacterium that is widely distributed across individuals and skin sites. Experimental characterization of this biosynthetic gene cluster resulted in identification of a new thiopeptide antibiotic, cutimycin. Analysis of individual human skin hair follicles revealed that cutimycin contributed to the ecology of the skin hair follicle microbiota and helped to reduce colonization of skin hair follicles by Staphylococcus species.
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页数:10
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