Nature Commun 11, 1539 (2020)
A Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis
D’Alessandro-Gabazza, C., Kobayashi, T., Yasuma, T., Toda, M., Kim, H., Fujimoto, H., Hataji, O., Takeshita, A., Nishihama, K., Okano, Y., Okano, Y., Nishii, Y., Tomaru, A., Fujiwara, K., D'Alessandro, V. F., Abdel-Hamid, A., Ren, Y., Pereira, G., Wright, C., Hernandez, A., Fields, C., Yau, P., Wang, S., Mizoguchi, A., Fukumura, M., Ohtsuka, J., Nosaka, T., Kataoka, K., Kondoh, Y., Wu, J., Kawagishi, H., Yano, Y., Mackie, R., Cann, I., and Gabazza, E. C.
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.