Functional divergence of a bacterial enzyme promotes healthy or acneic skin.
Functional divergence of a bacterial enzyme promotes healthy or acneic skin.
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DOI：
10.1038/s41467-023-43833-8
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发表时间：
2023-12-05
影响因子：
16.6
通讯作者：
Liu, George Y.
中科院分区：
文献类型：
--
作者：
Hajam, Irshad A.;Katiki, Madhusudhanarao;McNally, Randall;Lazaro-Diez, Maria;Kolar, Stacey;Chatterjee, Avradip;Gonzalez, Cesia;Paulchakrabarti, Mousumi;Choudhury, Biswa;Caldera, J. R.;Desmond, Trieu;Tsai, Chih-Ming;Du, Xin;Li, Huiying;Murali, Ramachandran;Liu, George Y.
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. Cutibacterium acnes phylotypes can be catalogued based on their association with acneic or healthy skin. Here, Hajam et al show that the functional divergence of a hyaluronidase enzyme expressed by the phylotypes is a major determinant of acne severity.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
与痤疮相关的人皮肤微生物组中的痤疮丙酸杆菌菌株群体。
影响因子：
6.5
作者：
Fitz-Gibbon, Sorel;Tomida, Shuta;Chiu, Bor-Han;Lin Nguyen;Du, Christine;Liu, Minghsun;Elashoff, David;Erfe, Marie C.;Loncaric, Anya;Kim, Jenny;Modlin, Robert L.;Miller, Jeff F.;Sodergren, Erica;Craft, Noah;Weinstock, George M.;Li, Huiying
通讯作者：
Li, Huiying
影响因子：
2.2
作者：
Cheong, Dae-Eun;Lee, Hae-In;So, Jae-Seong
通讯作者：
So, Jae-Seong
影响因子：
2.9
作者：
Joshi, Harshad V.;Jedrzejas, Mark J.;de Groot, Bert L.
通讯作者：
de Groot, Bert L.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH