Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development

Yuumi Nakamura; Hiroki Takahashi; Akiko Takaya; Yuzaburo Inoue; Yuki Katayama; Yoko Kusuya; Tatsuma Shoji; Sanami Takada; Seitaro Nakagawa; Rena Oguma; Nobuko Saito; Naoko Ozawa; Taiji Nakano; Fumiya Yamaide; Eishika Dissanayake; Shuichi Suzuki; Amer Villaruz; Saranyaraajan Varadarajan; Masanori Matsumoto; Tomoko Kobayashi; Michihiro Kono; Yasunori Sato; Masashi Akiyama; Michael Otto; Hiroyuki Matsue; Gabriel Núñez; Naoki Shimojo

doi:10.1126/SCITRANSLMED.AAY4068

Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development

Yuumi Nakamura, Hiroki Takahashi, Akiko Takaya, Yuzaburo Inoue, Yuki Katayama, Yoko Kusuya, Tatsuma Shoji, Sanami Takada, Seitaro Nakagawa, Rena Oguma, Nobuko Saito, Naoko Ozawa, Taiji Nakano, Fumiya Yamaide, Eishika Dissanayake, Shuichi Suzuki, Amer Villaruz, Saranyaraajan Varadarajan, Masanori Matsumoto, Tomoko KobayashiMichihiro Kono, Yasunori Sato, Masashi Akiyama, Michael Otto, Hiroyuki Matsue, Gabriel Núñez, Naoki Shimojo

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Abstract

Atopic dermatitis (AD) is commonly associated with colonization by Staphylococcus aureus in the affected skin. To understand the role of S. aureus in the development of AD, we performed whole-genome sequencing of S. aureus strains isolated from the cheek skin of 268 Japanese infants 1 and 6 months after birth. About 45% of infants were colonized with S. aureus at 1 month regardless of AD outcome. In contrast, skin colonization by S. aureus at 6 months of age increased the risk of developing AD. Acquisition of dysfunctional mutations in the S. aureus Agr quorum-sensing (QS) system was primarily observed in strains from 6-month-old infants who did not develop AD. Expression of a functional Agr system in S. aureus was required for epidermal colonization and the induction of AD-like inflammation in mice. Thus, retention of functional S. aureus agr virulence during infancy is associated with pathogen skin colonization and the development of AD.

Original language	English (US)
Article number	eaay4068
Journal	Science Translational Medicine
Volume	12
Issue number	551
DOIs	https://doi.org/10.1126/SCITRANSLMED.AAY4068
State	Published - Jul 2020
Externally published	Yes

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General Medicine

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Nakamura, Y., Takahashi, H., Takaya, A., Inoue, Y., Katayama, Y., Kusuya, Y., Shoji, T., Takada, S., Nakagawa, S., Oguma, R., Saito, N., Ozawa, N., Nakano, T., Yamaide, F., Dissanayake, E., Suzuki, S., Villaruz, A., Varadarajan, S., Matsumoto, M., ... Shimojo, N. (2020). Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development. Science Translational Medicine, 12(551), Article eaay4068. https://doi.org/10.1126/SCITRANSLMED.AAY4068

Nakamura, Y, Takahashi, H, Takaya, A, Inoue, Y, Katayama, Y, Kusuya, Y, Shoji, T, Takada, S, Nakagawa, S, Oguma, R, Saito, N, Ozawa, N, Nakano, T, Yamaide, F, Dissanayake, E, Suzuki, S, Villaruz, A, Varadarajan, S, Matsumoto, M, Kobayashi, T, Kono, M, Sato, Y, Akiyama, M, Otto, M, Matsue, H, Núñez, G & Shimojo, N 2020, 'Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development', Science Translational Medicine, vol. 12, no. 551, eaay4068. https://doi.org/10.1126/SCITRANSLMED.AAY4068

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title = "Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development",

abstract = "Atopic dermatitis (AD) is commonly associated with colonization by Staphylococcus aureus in the affected skin. To understand the role of S. aureus in the development of AD, we performed whole-genome sequencing of S. aureus strains isolated from the cheek skin of 268 Japanese infants 1 and 6 months after birth. About 45% of infants were colonized with S. aureus at 1 month regardless of AD outcome. In contrast, skin colonization by S. aureus at 6 months of age increased the risk of developing AD. Acquisition of dysfunctional mutations in the S. aureus Agr quorum-sensing (QS) system was primarily observed in strains from 6-month-old infants who did not develop AD. Expression of a functional Agr system in S. aureus was required for epidermal colonization and the induction of AD-like inflammation in mice. Thus, retention of functional S. aureus agr virulence during infancy is associated with pathogen skin colonization and the development of AD.",

author = "Yuumi Nakamura and Hiroki Takahashi and Akiko Takaya and Yuzaburo Inoue and Yuki Katayama and Yoko Kusuya and Tatsuma Shoji and Sanami Takada and Seitaro Nakagawa and Rena Oguma and Nobuko Saito and Naoko Ozawa and Taiji Nakano and Fumiya Yamaide and Eishika Dissanayake and Shuichi Suzuki and Amer Villaruz and Saranyaraajan Varadarajan and Masanori Matsumoto and Tomoko Kobayashi and Michihiro Kono and Yasunori Sato and Masashi Akiyama and Michael Otto and Hiroyuki Matsue and Gabriel N{\'u}{\~n}ez and Naoki Shimojo",

note = "Funding Information: This work was supported by JSPS KAKENHI grants 26713038 (Y.N.), 16H06252 (Y.N.), 16K15272 (A.T.), and 18H02832 (M.A.); MEXT KAKENHI grants 16K18671 (H.T.) and 16H06279 (H.T.); the Naito Foundation (Y.N.); the Takeda Science Foundation (H.T.); and AMED grants JP16ek0410029h0001 (Y.N., A.T., H.T., and N. Shimojo), JP18gm6010016h0002 (Y.N.), and 19gm0910002h0105 (M.A.). M.O. was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH (grant number ZIA AI000904-16). G.N. was supported by NIH grant AR069303 and a grant from the University of Michigan Host Microbiome Initiative (G.N.). N. Shimojo was supported by a grant from the Environmental Restoration and Conservation Agency of Japan in fiscal years 2012-2016. Y.N., H.T., A.T., S.N., and N. Shimojo were supported by the Institute for Global Prominent Research, Chiba University. This study was partly supported by Joint Usage/Research Program of Medical Mycology Research Center, Chiba University (20-19). Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works",

year = "2020",

month = jul,

doi = "10.1126/SCITRANSLMED.AAY4068",

language = "English (US)",

volume = "12",

journal = "Science Translational Medicine",

issn = "1946-6234",

publisher = "American Association for the Advancement of Science",

number = "551",

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TY - JOUR

T1 - Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development

AU - Nakamura, Yuumi

AU - Takahashi, Hiroki

AU - Takaya, Akiko

AU - Inoue, Yuzaburo

AU - Katayama, Yuki

AU - Kusuya, Yoko

AU - Shoji, Tatsuma

AU - Takada, Sanami

AU - Nakagawa, Seitaro

AU - Oguma, Rena

AU - Saito, Nobuko

AU - Ozawa, Naoko

AU - Nakano, Taiji

AU - Yamaide, Fumiya

AU - Dissanayake, Eishika

AU - Suzuki, Shuichi

AU - Villaruz, Amer

AU - Varadarajan, Saranyaraajan

AU - Matsumoto, Masanori

AU - Kobayashi, Tomoko

AU - Kono, Michihiro

AU - Sato, Yasunori

AU - Akiyama, Masashi

AU - Otto, Michael

AU - Matsue, Hiroyuki

AU - Núñez, Gabriel

AU - Shimojo, Naoki

N1 - Funding Information: This work was supported by JSPS KAKENHI grants 26713038 (Y.N.), 16H06252 (Y.N.), 16K15272 (A.T.), and 18H02832 (M.A.); MEXT KAKENHI grants 16K18671 (H.T.) and 16H06279 (H.T.); the Naito Foundation (Y.N.); the Takeda Science Foundation (H.T.); and AMED grants JP16ek0410029h0001 (Y.N., A.T., H.T., and N. Shimojo), JP18gm6010016h0002 (Y.N.), and 19gm0910002h0105 (M.A.). M.O. was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH (grant number ZIA AI000904-16). G.N. was supported by NIH grant AR069303 and a grant from the University of Michigan Host Microbiome Initiative (G.N.). N. Shimojo was supported by a grant from the Environmental Restoration and Conservation Agency of Japan in fiscal years 2012-2016. Y.N., H.T., A.T., S.N., and N. Shimojo were supported by the Institute for Global Prominent Research, Chiba University. This study was partly supported by Joint Usage/Research Program of Medical Mycology Research Center, Chiba University (20-19). Publisher Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

PY - 2020/7

Y1 - 2020/7

N2 - Atopic dermatitis (AD) is commonly associated with colonization by Staphylococcus aureus in the affected skin. To understand the role of S. aureus in the development of AD, we performed whole-genome sequencing of S. aureus strains isolated from the cheek skin of 268 Japanese infants 1 and 6 months after birth. About 45% of infants were colonized with S. aureus at 1 month regardless of AD outcome. In contrast, skin colonization by S. aureus at 6 months of age increased the risk of developing AD. Acquisition of dysfunctional mutations in the S. aureus Agr quorum-sensing (QS) system was primarily observed in strains from 6-month-old infants who did not develop AD. Expression of a functional Agr system in S. aureus was required for epidermal colonization and the induction of AD-like inflammation in mice. Thus, retention of functional S. aureus agr virulence during infancy is associated with pathogen skin colonization and the development of AD.

AB - Atopic dermatitis (AD) is commonly associated with colonization by Staphylococcus aureus in the affected skin. To understand the role of S. aureus in the development of AD, we performed whole-genome sequencing of S. aureus strains isolated from the cheek skin of 268 Japanese infants 1 and 6 months after birth. About 45% of infants were colonized with S. aureus at 1 month regardless of AD outcome. In contrast, skin colonization by S. aureus at 6 months of age increased the risk of developing AD. Acquisition of dysfunctional mutations in the S. aureus Agr quorum-sensing (QS) system was primarily observed in strains from 6-month-old infants who did not develop AD. Expression of a functional Agr system in S. aureus was required for epidermal colonization and the induction of AD-like inflammation in mice. Thus, retention of functional S. aureus agr virulence during infancy is associated with pathogen skin colonization and the development of AD.

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U2 - 10.1126/SCITRANSLMED.AAY4068

DO - 10.1126/SCITRANSLMED.AAY4068

M3 - Article

C2 - 32641488

AN - SCOPUS:85087660304

SN - 1946-6234

VL - 12

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 551

M1 - eaay4068

ER -

Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development

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