A Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis

Corina N D'Alessandro-Gabazza; Tetsu Kobayashi; Taro Yasuma; Masaaki Toda; Heejin Kim; Hajime Fujimoto; Osamu Hataji; Atsuro Takeshita; Kota Nishihama; Tomohito Okano; Yuko Okano; Yoichi Nishii; Atsushi Tomaru; Kentaro Fujiwara; Valeria Fridman D'Alessandro; Ahmed M Abdel-Hamid; Yudong Ren; Gabriel V Pereira; Christy L Wright; Alvaro Hernandez; Christopher J Fields; Peter M Yau; Shujie Wang; Akira Mizoguchi; Masayuki Fukumura; Junpei Ohtsuka; Tetsuya Nosaka; Kensuke Kataoka; Yasuhiro Kondoh; Jing Wu; Hirokazu Kawagishi; Yutaka Yano; Roderick I Mackie; Isaac Cann; Esteban C Gabazza

doi:10.1038/s41467-020-15344-3

A Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis

Nat Commun. 2020 Mar 24;11(1):1539. doi: 10.1038/s41467-020-15344-3.

Authors

Corina N D'Alessandro-Gabazza^#^{1

2

3}, Tetsu Kobayashi^#⁴, Taro Yasuma^#^{1

2

5}, Masaaki Toda^#^{1

2}, Heejin Kim^#³, Hajime Fujimoto⁴, Osamu Hataji⁶, Atsuro Takeshita^{1

5}, Kota Nishihama⁵, Tomohito Okano⁴, Yuko Okano^{1

5}, Yoichi Nishii⁶, Atsushi Tomaru⁴, Kentaro Fujiwara^{4

6}, Valeria Fridman D'Alessandro¹, Ahmed M Abdel-Hamid³, Yudong Ren^{3

7}, Gabriel V Pereira^{3

8}, Christy L Wright⁹, Alvaro Hernandez⁹, Christopher J Fields⁹, Peter M Yau⁹, Shujie Wang¹⁰, Akira Mizoguchi¹⁰, Masayuki Fukumura^{11

12}, Junpei Ohtsuka^{11

12}, Tetsuya Nosaka¹², Kensuke Kataoka¹³, Yasuhiro Kondoh¹³, Jing Wu¹⁴, Hirokazu Kawagishi^{14

15}, Yutaka Yano⁵, Roderick I Mackie^{3

8

16}, Isaac Cann^{17

18

19

20

21}, Esteban C Gabazza^{22

23

24}

Affiliations

¹ Department of Immunology, Mie University Faculty and Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
² Center for Intractable Diseases, Mie University, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
³ Carl R. Woese Institute for Genomic Biology (Microbiome Metabolic Engineering), University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁴ Department of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
⁵ Department of Diabetes and Endocrinology, Mie University Faculty and Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
⁶ Respiratory Center, Matsusaka Municipal Hospital, Tonomachi 1550, Matsusaka, Mie, 515-8544, Japan.
⁷ The School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁸ Department of Animal Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁹ W.M. Keck Center for Functional and Comparative Genomics, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹⁰ Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Tsu, Mie, 14101, Japan.
¹¹ BioComo Incorporation, Komono, Mie, 510-1233, Japan.
¹² Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.
¹³ Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi, 489-8642, Japan.
¹⁴ Research Institute of Green Science and Technology, Graduate School of Agriculture, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529, Japan.
¹⁵ Green Chemistry Research Division, Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529, Japan.
¹⁶ Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹⁷ Carl R. Woese Institute for Genomic Biology (Microbiome Metabolic Engineering), University of Illinois at Urbana-Champaign, Urbana, IL, USA. [email protected].
¹⁸ The School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. [email protected].
¹⁹ Department of Animal Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA. [email protected].
²⁰ Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA. [email protected].
²¹ Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. [email protected].
²² Department of Immunology, Mie University Faculty and Graduate School of Medicine, Edobashi 2-174, Tsu, Mie, 514-8507, Japan. [email protected].
²³ Center for Intractable Diseases, Mie University, Edobashi 2-174, Tsu, Mie, 514-8507, Japan. [email protected].
²⁴ Carl R. Woese Institute for Genomic Biology (Microbiome Metabolic Engineering), University of Illinois at Urbana-Champaign, Urbana, IL, USA. [email protected].

^# Contributed equally.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown etiology; however, apoptosis of lung alveolar epithelial cells plays a role in disease progression. This intractable disease is associated with increased abundance of Staphylococcus and Streptococcus in the lungs, yet their roles in disease pathogenesis remain elusive. Here, we report that Staphylococcus nepalensis releases corisin, a peptide conserved in diverse staphylococci, to induce apoptosis of lung epithelial cells. The disease in mice exhibits acute exacerbation after intrapulmonary instillation of corisin or after lung infection with corisin-harboring S. nepalensis compared to untreated mice or mice infected with bacteria lacking corisin. Correspondingly, the lung corisin levels are significantly increased in human IPF patients with acute exacerbation compared to patients without disease exacerbation. Our results suggest that bacteria shedding corisin are involved in acute exacerbation of IPF, yielding insights to the molecular basis for the elevation of staphylococci in pulmonary fibrosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Animals
Apoptosis / immunology
Apoptosis Regulatory Proteins / analysis
Apoptosis Regulatory Proteins / immunology*
Apoptosis Regulatory Proteins / metabolism
Bacterial Proteins / analysis
Bacterial Proteins / immunology*
Bacterial Proteins / metabolism
Bronchoalveolar Lavage Fluid / chemistry
Bronchoalveolar Lavage Fluid / immunology
Disease Models, Animal
Epithelial Cells / immunology
Epithelial Cells / pathology
Female
Healthy Volunteers
Humans
Idiopathic Pulmonary Fibrosis / genetics
Idiopathic Pulmonary Fibrosis / immunology*
Idiopathic Pulmonary Fibrosis / microbiology
Idiopathic Pulmonary Fibrosis / pathology
Lung / immunology
Lung / microbiology
Lung / pathology
Macrophages / immunology
Male
Mice
Mice, Transgenic
Peptides / analysis
Peptides / immunology*
Peptides / metabolism
Staphylococcus / immunology*
Staphylococcus / metabolism
Staphylococcus / pathogenicity
Symptom Flare Up
T-Lymphocytes, Regulatory / immunology
Transforming Growth Factor beta1 / genetics
Transforming Growth Factor beta1 / immunology

Substances

Apoptosis Regulatory Proteins
Bacterial Proteins
Peptides
TGFB1 protein, human
Transforming Growth Factor beta1

Supplementary concepts

Staphylococcus nepalensis