TY - JOUR
T1 - A Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis
AU - D’alessandro-gabazza, Corina N.
AU - Kobayashi, Tetsu
AU - Yasuma, Taro
AU - Toda, Masaaki
AU - Kim, Heejin
AU - Fujimoto, Hajime
AU - Hataji, Osamu
AU - Takeshita, Atsuro
AU - Nishihama, Kota
AU - Okano, Tomohito
AU - Okano, Yuko
AU - Nishii, Yoichi
AU - Tomaru, Atsushi
AU - Fujiwara, Kentaro
AU - D’alessandro, Valeria Fridman
AU - Abdel-hamid, Ahmed M.
AU - Ren, Yudong
AU - Pereira, Gabriel V.
AU - Wright, Christy L.
AU - Hernandez, Alvaro
AU - Fields, Christopher J.
AU - Yau, Peter M.
AU - Wang, Shujie
AU - Mizoguchi, Akira
AU - Fukumura, Masayuki
AU - Ohtsuka, Junpei
AU - Nosaka, Tetsuya
AU - Kataoka, Kensuke
AU - Kondoh, Yasuhiro
AU - Wu, Jing
AU - Kawagishi, Hirokazu
AU - Yano, Yutaka
AU - Mackie, Roderick I.
AU - Cann, Isaac
AU - Gabazza, Esteban C.
N1 - Funding Information:
This research was supported in part by the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Kakenhi No 17K08442 and 18K08175), and in part by funding support for the Microbiome Metabolic Engineering Theme (Carl R. Woose Institute for Genomic Biology) and by the College of Agricultural, Consumer and Environmental Sciences Office of International Programs, University of Illinois at Urbana-Champaign. The funders had no role in study design, data analysis, decision to publish, or preparation of the manuscript. We would like to thank Lou Ann Miller (Frederick Seitz Material Research Lab, UIUC) and Miyuki Ieda (Mie University School of Medicine) for technical support.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
KW - microbiome
KW - translational research
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U2 - 10.1038/s41467-020-15344-3
DO - 10.1038/s41467-020-15344-3
M3 - Article
C2 - 32210242
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1539
ER -