Elodie Ramond, A. Lepissier, Xiongqi Ding, C. Bouvier, X. Tan, Daniel Euphrasie, Pierre Monbernard, M. Dupuis, B. Saubaméa, I. Nemazanyy, X. Nassif, A. Ferroni, I. Sermet-Gaudelus, A. Charbit, Mathieu Coureuil, A. Jamet
{"title":"肺适应性金黄色葡萄球菌分离与功能失调的agr系统触发促炎反应。","authors":"Elodie Ramond, A. Lepissier, Xiongqi Ding, C. Bouvier, X. Tan, Daniel Euphrasie, Pierre Monbernard, M. Dupuis, B. Saubaméa, I. Nemazanyy, X. Nassif, A. Ferroni, I. Sermet-Gaudelus, A. Charbit, Mathieu Coureuil, A. Jamet","doi":"10.1093/infdis/jiac191","DOIUrl":null,"url":null,"abstract":"BACKGROUND\nStaphylococcus aureus (Sa) dominates the lung microbiota of Cystic Fibrosis (CF) children and persistent clones are able to establish chronic infection for years, having a direct deleterious impact on lung function. However, in this context, the exact contribution of Sa to the decline in respiratory function in CF children is not elucidated.\n\n\nMETHODS\nTo investigate the contribution of persistent S. aureus clones in CF disease, we undertook the analysis of sequential isogenic isolates recovered from 15 young CF patients.\n\n\nRESULTS\nUsing an Air-Liquid infection model, we observed a strong correlation between Sa adaption in the lung (late isolates), low toxicity and pro-inflammatory cytokine secretion. Conversely, early isolates appeared to be highly cytotoxic but did not promote cytokine secretion. We found that cytokine secretion was dependent on Staphylococcal protein A (Spa), which was selectively expressed in late compared to early isolates as a consequence of dysfunctional agr quorum-sensing system. Finally, we demonstrated the involvement of TNF-α receptor 1 signaling in the inflammatory response of airway epithelial cells to these lung-adapted Sa isolates.\n\n\nCONCLUSION\nOur results suggest an unexpected direct role of bacterial lung adaptation in the progression of chronic lung disease by promoting a pro-inflammatory response through acquired agr dysfunction.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"5","resultStr":"{\"title\":\"Lung-adapted Staphylococcus aureus isolates with dysfunctional agr system trigger a proinflammatory response.\",\"authors\":\"Elodie Ramond, A. Lepissier, Xiongqi Ding, C. Bouvier, X. Tan, Daniel Euphrasie, Pierre Monbernard, M. Dupuis, B. Saubaméa, I. Nemazanyy, X. Nassif, A. Ferroni, I. Sermet-Gaudelus, A. Charbit, Mathieu Coureuil, A. Jamet\",\"doi\":\"10.1093/infdis/jiac191\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"BACKGROUND\\nStaphylococcus aureus (Sa) dominates the lung microbiota of Cystic Fibrosis (CF) children and persistent clones are able to establish chronic infection for years, having a direct deleterious impact on lung function. However, in this context, the exact contribution of Sa to the decline in respiratory function in CF children is not elucidated.\\n\\n\\nMETHODS\\nTo investigate the contribution of persistent S. aureus clones in CF disease, we undertook the analysis of sequential isogenic isolates recovered from 15 young CF patients.\\n\\n\\nRESULTS\\nUsing an Air-Liquid infection model, we observed a strong correlation between Sa adaption in the lung (late isolates), low toxicity and pro-inflammatory cytokine secretion. Conversely, early isolates appeared to be highly cytotoxic but did not promote cytokine secretion. We found that cytokine secretion was dependent on Staphylococcal protein A (Spa), which was selectively expressed in late compared to early isolates as a consequence of dysfunctional agr quorum-sensing system. Finally, we demonstrated the involvement of TNF-α receptor 1 signaling in the inflammatory response of airway epithelial cells to these lung-adapted Sa isolates.\\n\\n\\nCONCLUSION\\nOur results suggest an unexpected direct role of bacterial lung adaptation in the progression of chronic lung disease by promoting a pro-inflammatory response through acquired agr dysfunction.\",\"PeriodicalId\":22572,\"journal\":{\"name\":\"The Indonesian Journal of Infectious Diseases\",\"volume\":\"11 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"5\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Indonesian Journal of Infectious Diseases\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/infdis/jiac191\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Indonesian Journal of Infectious Diseases","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/infdis/jiac191","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Lung-adapted Staphylococcus aureus isolates with dysfunctional agr system trigger a proinflammatory response.
BACKGROUND
Staphylococcus aureus (Sa) dominates the lung microbiota of Cystic Fibrosis (CF) children and persistent clones are able to establish chronic infection for years, having a direct deleterious impact on lung function. However, in this context, the exact contribution of Sa to the decline in respiratory function in CF children is not elucidated.
METHODS
To investigate the contribution of persistent S. aureus clones in CF disease, we undertook the analysis of sequential isogenic isolates recovered from 15 young CF patients.
RESULTS
Using an Air-Liquid infection model, we observed a strong correlation between Sa adaption in the lung (late isolates), low toxicity and pro-inflammatory cytokine secretion. Conversely, early isolates appeared to be highly cytotoxic but did not promote cytokine secretion. We found that cytokine secretion was dependent on Staphylococcal protein A (Spa), which was selectively expressed in late compared to early isolates as a consequence of dysfunctional agr quorum-sensing system. Finally, we demonstrated the involvement of TNF-α receptor 1 signaling in the inflammatory response of airway epithelial cells to these lung-adapted Sa isolates.
CONCLUSION
Our results suggest an unexpected direct role of bacterial lung adaptation in the progression of chronic lung disease by promoting a pro-inflammatory response through acquired agr dysfunction.