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

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.

Staphylococcus nepalensis, a commensal of the oral microbiota of domestic cats, is a reservoir of transferrable antimicrobial resistance

“… S. nepalensis is just one example of this interconnectivity: although typically found within the microbiota of specific animals, these usually overlooked species can occasionally be isolated from human clinical material [9, 10]. Therefore, we believe that the results presented herein highlight that no Staphylococcus should be neglected during surveillance and epidemiological studies, as some atypical and underestimated species, such as S.…”

“…Nearly two decades after the discovery of S. nepalensis [8], this species has been occasionally isolated from a variety of clinical samples from humans, as well as from animals, such as goats, cows, guano of bats, pig skin and a squirrel monkey’s gastrointestinal tract [8–10, 22]. A recent study isolated Staphylococcus from conjunctival sacs, nares, skin, anus and wounds from thousands of cats [23].…”

“…A recent study suggested that the production of the pro-apoptotic peptide corisin by an S. nepalensis strain may contribute to the progress of idiopathic pulmonary fibrosis [10]. However, studies focusing on S.…”

De Novo T790M Mutation in an L858R Epidermal Growth Factor Receptor Mutant-Associated Lung Adenocarcinoma

“…Micro-CT (Latheta LCT-200, Hitachi Aloka Medical, Tokyo, Japan) was used to screen the presence of lung tumors in the mouse models. Acquisition of data was performed with mice in prone position under isoflurane inhalation anesthesia with respiratory gating as previously described [ 27 , 28 , 29 ].…”

Low-Dose of Intrapulmonary Pirfenidone Improves Human Transforming Growth Factorβ1-Driven Lung Fibrosis

“…The transgenic mouse overexpresses the human TGFβ1 transgene specifically in the lung and has a high total and active human TGFβ1 in the systemic circulation and the lungs. The precise mechanism of TGFβ1 activation in this lung fibrosis mouse model is unclear; however, indirect evidence suggests that the lung microbiome plays a role in TGFβ1 activation in the model (D'Alessandro-Gabazza et al, 2020).…”