Burkholderia cenocepacia K56-2 trimeric autotransporter adhesin BcaA binds TNFR1 and contributes to induce airway inflammation.
Chronic lung disease caused by persistent bacterial infections is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). CF pathogens acquire antibiotic resistance, overcome host defenses, and impose uncontrolled inflammation that ultimately may cause permanent damage of lungs' airways. Among the multiple CF-associated pathogens, Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria have become prominent contributors of disease progression. Here, we demonstrate that BcaA, a trimeric autotransporter adhesin (TAA) from the epidemic strain B. cenocepacia K56-2, is a tumor necrosis factor receptor 1-interacting protein able to regulate components of the tumor necrosis factor signaling pathway and ultimately leading to a significant production of the proinflammatory cytokine IL-8. Notably, this study is the first to demonstrate that a protein belonging to the TAA family is involved in the induction of the inflammatory response during B. cenocepacia infections, contributing to the success of the pathogen. Moreover, our results reinforce the relevance of the TAA BcaA as a multifunctional protein with a major role in B. cenocepacia virulence.
Institute for Bioengineering and Biosciences (iBB), Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.
Dalila
D
Mil-Homens
Centro de Química Física Molecular and Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.
Sandra N
SN
Pinto
Instituto de Tecnologia Química e Biológica - ITQB, Universidade Nova de Lisboa, Oeiras, Portugal.
Rute G
RG
Matos
Instituto de Tecnologia Química e Biológica - ITQB, Universidade Nova de Lisboa, Oeiras, Portugal.
Cecília
C
Arraiano
Institute for Bioengineering and Biosciences (iBB), Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.|Department of Bioengineering, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.
Arsenio M
AM
Fialho
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D001422:Bacterial Adhesion; D019121:Burkholderia Infections / Q000382:microbiology*; D057508:Burkholderia cenocepacia / Q000502:physiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D011014:Pneumonia / Q000382:microbiology*; D011485:Protein Binding; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction
D018829:Adhesins, Bacterial; D047888:Receptors, Tumor Necrosis Factor, Type I