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 HernandezChristopher 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

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish (US)
Article number1539
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

Keywords

  • microbiome
  • translational research

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

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