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 () and Esteban C. Gabazza ()
Additional contact information
Corina N. D’Alessandro-Gabazza: Mie University Faculty and Graduate School of Medicine
Tetsu Kobayashi: Mie University Faculty and Graduate School of Medicine
Taro Yasuma: Mie University Faculty and Graduate School of Medicine
Masaaki Toda: Mie University Faculty and Graduate School of Medicine
Heejin Kim: University of Illinois at Urbana–Champaign
Hajime Fujimoto: Mie University Faculty and Graduate School of Medicine
Osamu Hataji: Respiratory Center, Matsusaka Municipal Hospital
Atsuro Takeshita: Mie University Faculty and Graduate School of Medicine
Kota Nishihama: Mie University Faculty and Graduate School of Medicine
Tomohito Okano: Mie University Faculty and Graduate School of Medicine
Yuko Okano: Mie University Faculty and Graduate School of Medicine
Yoichi Nishii: Respiratory Center, Matsusaka Municipal Hospital
Atsushi Tomaru: Mie University Faculty and Graduate School of Medicine
Kentaro Fujiwara: Mie University Faculty and Graduate School of Medicine
Valeria Fridman D’Alessandro: Mie University Faculty and Graduate School of Medicine
Ahmed M. Abdel-Hamid: University of Illinois at Urbana–Champaign
Yudong Ren: University of Illinois at Urbana–Champaign
Gabriel V. Pereira: University of Illinois at Urbana–Champaign
Christy L. Wright: University of Illinois at Urbana–Champaign
Alvaro Hernandez: University of Illinois at Urbana–Champaign
Christopher J. Fields: University of Illinois at Urbana–Champaign
Peter M. Yau: University of Illinois at Urbana–Champaign
Shujie Wang: Mie University Graduate School of Medicine
Akira Mizoguchi: Mie University Graduate School of Medicine
Masayuki Fukumura: BioComo Incorporation
Junpei Ohtsuka: BioComo Incorporation
Tetsuya Nosaka: Mie University Graduate School of Medicine
Kensuke Kataoka: Department of Respiratory Medicine and Allergy, Tosei General Hospital
Yasuhiro Kondoh: Department of Respiratory Medicine and Allergy, Tosei General Hospital
Jing Wu: Shizuoka University
Hirokazu Kawagishi: Shizuoka University
Yutaka Yano: Mie University Faculty and Graduate School of Medicine
Roderick I. Mackie: University of Illinois at Urbana–Champaign
Isaac Cann: University of Illinois at Urbana–Champaign
Esteban C. Gabazza: Mie University Faculty and Graduate School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15344-3

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