Burkholderia cenocepacia K56‐2 trimeric autotransporter adhesin BcaA binds TNFR1 and contributes to induce airway inflammation

Abstract

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.

Burkholderia cenocepacia–host cell contact controls the transcription activity of the trimeric autotransporter adhesin BCAM2418 gene

“…This fact enhances the assumption that is the physical recognition of a cellular target component by B. cenocepacia that leads to the increased expression of this TAA mRNA. This hypothesis is reinforced by previous studies that point out the interaction of B. cenocepacia and other Bcc species with extracellular molecules of airway cell lines as an essential set point of infection (Mil‐Homens et al, ; Pacello, D'Orazio, & Battistoni, ).…”

“…B. cenocepacia epidemic strains of the ET‐12 lineage are reported to have 7 TAA‐encoding genes (Mil‐Homens & Fialho, ; Mil‐Homens et al, ). Mil‐Homens and colleagues unveil the multifunctional functions of two B. cenocepacia K56‐2 TAAs (BCAM0223 and BcaA) clustered together in chromosome 2 (Mil‐Homens & Fialho, , ; Mil‐Homens et al, , ). The existence of these surface proteins contributes to the overall pathogenicity of this bacterium (Mil‐Homens & Fialho, ; Mil‐Homens et al, ).…”

“…B. cenocepacia J2315 possess 7 TAA‐encoding genes distributed between chromosome 2 ( bcaA, BCAM0219, 0223, 1115, and 2418 ) and 3 ( BCAS0236 and 0335 ) (Mil‐Homens & Fialho, , ; Mil‐Homens, Leça, Fernandes, Pinto, & Fialho, ). They have been implicated in the binding to a considerable set of molecules, such as host cell receptors, components of the extracellular matrix or even other TAAs (El‐Kirat‐Chatel, Mil‐Homens, Beaussart, Fialho, & Dufrêne, ; Mil‐Homens, Pinto, Matos, Arraiano, & Fialho, ). Results showed that TAAs are involved in several virulence‐associated features, such as biofilm formation, evasion to host immune system, motility, invasion of host cells, hemagglutination, and induction of inflammation (Mil‐Homens & Fialho, , ; Mil‐Homens et al, , ).…”

Burkholderia cenocepacia transcriptome during the early contacts with giant plasma membrane vesicles derived from live bronchial epithelial cells

“…Also, adhesin-mediated binding to cytokeratin 13 seems to be absolutely necessary for subsequent invasion and transmigration across the epithelium 10 , 63 , 65 . B. cenocepacia TAAs have been studied in detail during the past years, and are known to be multifunctional proteins involved in many virulence related traits like biofilm formation, motility, adhesion and invasion of host cells 9 , 11 , 13 , 66 , 67 . The expression of BCAM2418 and BCAS0236 TAA encoding genes during the early stages of B. cenocepacia infection was demonstrated in a recent work 12 .…”

A genomic island in Brucella involved in the adhesion to host cells: Identification of a new adhesin and a translocation factor

“…Adhesins are responsible for pathogen persistence causing, among other symptoms, tissue inflammation in the host. Gut mucosa, lungs and bladder are some examples of inflammation mediated by adhesin immune activation (Conover et al, 2016; Mil‐Homens, Pinto, Matos, Arraiano, & Fialho, 2017; Moore, Boren, & Solnick, 2011; Palmela et al, 2018). The cytoskeleton is intrinsically involved in inflammation and its plasticity is an important component of host cells.…”