2026-08-29T10:10:17Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/235052024-11-29T00:48:53Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Mateu-Borrás, Margalida author Gonzalez-Alsina, Alex author Doménech-Sánchez, Antonio author Querol-Garcia, Javier author Fernandez, Francisco J author Cristina Vega, Ma author Alberti, Sebastian author 2022-12-31 Cystic fibrosis (CF) disease is characterized by an intense airway inflammatory response mediated by neutrophils and chronic respiratory infections caused by P. aeruginosa. High levels of the complement component C5a, the strongest neutrophil chemoattractant molecule, are commonly found in the CF lung and have been associated with a worsening of the disease. In this study, we investigated how the isolates from CF patients modulate the levels of C5a and identified the bacterial factors involved. We demonstrated that most isolates from airway chronic infections induce the production and accumulation of C5a, an effect attributable to the loss of C5a cleavage by the exoproteases alkaline protease (AprA) and elastase B (LasB). Furthermore, we found that lack of the bacterial protease-dependent C5a degradation is due to mutations in the master regulator LasR. Thus, complementation of a non-C5a-cleaving CF isolate with a functional wild-type LasR restored its ability to express both proteases, cleave C5a and reduce neutrophil recruitment in vitro. These findings suggest that the non-cleaving C5a phenotype acquired by the LasR variants frequently isolated in CF patients may account for the strong neutrophilia and general neutrophil dysfunction predisposing toward increased inflammation and reduced bacterial clearance described in CF patients. Mateu-Borras M, Gonzalez-Alsina A, Domenech-Sanchez A, Querol-Garcia J, Fernandez FJ, Vega MC, et al. Pseudomonas aeruginosa adaptation in cystic fibrosis patients increases C5a levels and promotes neutrophil recruitment. Virulence. 2022 Dec 31;13(1):215-24. 10.1080/21505594.2022.2028484 2150-5608 2150-5594 Virulence https://hdl.handle.net/20.500.13003/19781 35094639 L2014873217 2-s2.0-85123904606 https://hdl.handle.net/20.500.12105/23505 748380100001 C5a alkaline protease A elastase B lasR cystic fibrosis Pseudomonas aeruginosa adaptation in cystic fibrosis patients increases C5a levels and promotes neutrophil recruitment