2023-12-20 カリフォルニア大学サンディエゴ校(UCSD)
◆これにより、にきびの原因を的確に対処する治療法を開発することが期待されています。研究者たちは、バクテリアの遺伝的要因を理解することで、標的型のにきび治療法の開発に寄与できるとし、将来的な治療法の可能性を追求しています。
<関連情報>
- https://today.ucsd.edu/story/groundbreaking-research-paves-the-way-for-acne-vaccine
- https://www.nature.com/articles/s41467-023-43833-8
- https://insight.jci.org/articles/view/124687
細菌酵素の機能的分岐が健康な肌とニキビ肌を促進する Functional divergence of a bacterial enzyme promotes healthy or acneic skin
Irshad A. Hajam,Madhusudhanarao Katiki,Randall McNally,María Lázaro-Díez,Stacey Kolar,Avradip Chatterjee,Cesia Gonzalez,Mousumi Paulchakrabarti,Biswa Choudhury,J. R. Caldera,Trieu Desmond,Chih-Ming Tsai,Xin Du,Huiying Li,Ramachandran Murali & George Y. Liu
Nature Communications Published:05 December 2023
DOI:https://doi.org/10.1038/s41467-023-43833-8
Abstract
Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated with acne, whereas others are associated with healthy skin. Here we investigate if the evolution of a C. acnes enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by C. acnes strains, HylA and HylB, demonstrate remarkable clinical correlation with acne or health. We show that HylA is strongly pro-inflammatory, and HylB is modestly anti-inflammatory in a murine (female) acne model. Structural and phylogenic studies suggest that the enzymes evolved from a common hyaluronidase that acquired distinct enzymatic activity. Health-associated HylB degrades hyaluronic acid (HA) exclusively to HA disaccharides leading to reduced inflammation, whereas HylA generates large-sized HA fragments that drive robust TLR2-dependent pathology. Replacing an amino acid, Serine to Glycine near the HylA catalytic site enhances the enzymatic activity of HylA and produces an HA degradation pattern intermediate to HylA and HylB. Selective targeting of HylA using peptide vaccine or inhibitors alleviates acne pathology. We suggest that the functional divergence of HylA and HylB is a major driving force behind C. acnes health- and acne- phenotype and propose targeting of HylA as an approach for acne therapy.
プロピオニバクテリウム・アクネスによる免疫病理は健康と病気の関連性と相関する Propionibacterium acnes–induced immunopathology correlates with health and disease association
Stacey L. Kolar,Chih-Ming Tsai,Juan Torres,Xuemo Fan,Huiying Li,and George Y. Liu
JCI Insight Published March 7, 2019
DOI:https://doi.org/10.1172/jci.insight.124687
Abstract
Genomic studies revealed the existence of health- and acne-associated P. acnes strains and suggested novel approaches for broadening understanding of acne vulgaris. However, clinical association of P. acnes with disease or health has yet to be corroborated experimentally. Current animal models of acne do not closely mimic human disease and have unclear translational value. We have developed a murine model of acne by combining P. acnes inoculation with topical application of a synthetic human sebum. We showed that human sebum promoted persistence of intradermally injected P. acnes with little loss of viability after 1 week and permitted use of more physiologic inoculums. Application of acne-associated P. acnes RT4/5 strains led to development of moderate to severe skin pathology compared with application of health-associated type II P. acnes strains (RT2/6). RT4/5 P. acnes strains uniformly induced higher levels of KC (IL-8), IL-1α, IL-1β, and IL-6 in vitro and in vivo compared with type II P. acnes strains. Overall, our data provide immunopathologic corroboration of health and disease association of clinical P. acnes strains and inform on a platform to query putative virulence factors uncovered by genomic studies.
