scholarly journals 159* Proteomic analysis of the Burkholderia cepacia complex outer membrane proteins involved in adhesion to lung epithelial cells

2011 ◽  
Vol 10 ◽  
pp. S40
Author(s):  
M.M. Thomas ◽  
S. Carberry ◽  
S. Doyle ◽  
M. Callaghan ◽  
S. McClean
Keyword(s):  
Membrane Proteins ◽  
Epithelial Cells ◽  
Outer Membrane ◽  
Proteomic Analysis ◽  
Burkholderia Cepacia ◽  
Outer Membrane Proteins ◽  
Lung Epithelial Cells ◽  
Burkholderia Cepacia Complex ◽  
Lung Epithelial

scholarly journals Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

2016 ◽  
Vol 84 (5) ◽  
pp. 1424-1437 ◽  
Author(s):  
Siobhán McClean ◽  
Marc E. Healy ◽  
Cassandra Collins ◽  
Stephen Carberry ◽  
Luke O'Shaughnessy ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Burkholderia Cepacia ◽  
Therapeutic Option ◽  
Lung Epithelial Cells ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Content Type ◽  
Lung Epithelial ◽  
Proteomics Approach

Members of theBurkholderia cepaciacomplex (Bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (CF), resulting in a gradual lung function decline and, ultimately, patient death. The Bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of Bcc bacteria to lung epithelial cells. Fourteen proteins were reproducibly identified by two-dimensional gel electrophoresis from four Bcc strains representative of two Bcc species:Burkholderia cenocepacia, the most virulent, andB. multivorans, the most frequently acquired. Seven proteins were identified in both species, but only two were common to all four strains, linocin and OmpW. Both proteins were selected based on previously reported data on these proteins in other species.Escherichia colistrains expressing recombinant linocin and OmpW showed enhanced attachment (4.2- and 3.9-fold) to lung cells compared to the control, confirming that both proteins are involved in host cell attachment. Immunoproteomic analysis using serum from Bcc-colonized CF patients confirmed that both proteins elicit potent humoral responsesin vivo. Mice immunized with either recombinant linocin or OmpW were protected fromB. cenocepaciaandB. multivoranschallenge. Both antigens induced potent antigen-specific antibody responses and stimulated strong cytokine responses. In conclusion, our approach identified adhesins that induced excellent protection against two Bcc species and are promising vaccine candidates for a multisubunit vaccine. Furthermore, this study highlights the potential of our proteomics approach to identify potent antigens against other difficult pathogens.

scholarly journals Thinking Outside the Bug: Targeting Outer Membrane Proteins for Burkholderia Vaccines

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 495
Author(s):  
Megan E. Grund ◽  
Jeon Soo ◽  
Christopher K. Cote ◽  
Rita Berisio ◽  
Slawomir Lukomski
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Burkholderia Cepacia ◽  
Respiratory Infections ◽  
Outer Membrane Proteins ◽  
Burkholderia Cepacia Complex ◽  
Resistant Bacteria ◽  
Respiratory Pathogens ◽  
Significant Treatment ◽  
Gram Negative

Increasing antimicrobial resistance due to misuse and overuse of antimicrobials, as well as a lack of new and innovative antibiotics in development has become an alarming global threat. Preventative therapeutics, like vaccines, are combative measures that aim to stop infections at the source, thereby decreasing the overall use of antibiotics. Infections due to Gram-negative pathogens pose a significant treatment challenge because of substantial multidrug resistance that is acquired and spread throughout the bacterial population. Burkholderia spp. are Gram-negative intrinsically resistant bacteria that are responsible for environmental and nosocomial infections. The Burkholderia cepacia complex are respiratory pathogens that primarily infect immunocompromised and cystic fibrosis patients, and are acquired through contaminated products and equipment, or via patient-to-patient transmission. The Burkholderia pseudomallei complex causes percutaneous wound, cardiovascular, and respiratory infections. Transmission occurs through direct exposure to contaminated water, water-vapors, or soil, leading to the human disease melioidosis, or the equine disease glanders. Currently there is no licensed vaccine against any Burkholderia pathogen. This review will discuss Burkholderia vaccine candidates derived from outer membrane proteins, OmpA, OmpW, Omp85, and Bucl8, encompassing their structures, conservation, and vaccine formulation.

scholarly journals Burkholderia cepacia complex: epithelial cell–pathogen confrontations and potential for therapeutic intervention

2009 ◽  
Vol 58 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Siobhán McClean ◽  
Máire Callaghan
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Burkholderia Cepacia ◽  
Opportunistic Pathogen ◽  
Lung Epithelial Cells ◽  
Burkholderia Cepacia Complex ◽  
Antibiotic Resistant ◽  
Therapeutic Implications ◽  
Lung Epithelial ◽  
Epithelial Cell Surface

Burkholderia cepacia complex (Bcc) is an important and virulent pathogen in cystic fibrosis patients. The interactions between this pathogen and the host lung epithelium are being widely investigated but remain to be elucidated. The complex is very versatile and its interactions with the lung epithelial cells are many and varied. The first steps in the interaction are penetration of the mucosal blanket and subsequent adherence to the epithelial cell surface. A range of epithelial receptors have been reported to bind to Bcc. The next step in pathogenesis is the invasion of the lung epithelial cell and also translocation across the epithelium to the serosal side. Furthermore, pathogenesis is mediated by a range of virulence factors that elicit their effects on the epithelial cells. This review outlines these interactions and examines the therapeutic implications of understanding the mechanisms of pathogenesis of this difficult, antibiotic-resistant, opportunistic pathogen.

β-Barrel outer membrane proteins suppress mTORC2 activation and induce autophagic responses

2018 ◽  
Vol 11 (558) ◽  
pp. eaat7493 ◽  
Author(s):  
Anu Chaudhary ◽  
Cassandra Kamischke ◽  
Mara Leite ◽  
Melissa A. Altura ◽  
Loren Kinman ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Epithelial Cells ◽  
Outer Membrane ◽  
Cellular Response ◽  
Tertiary Structure ◽  
Inflammatory Responses ◽  
Outer Membrane Proteins ◽  
Cell Surface Receptor ◽  
Mouse Bone Marrow ◽  
Endosomal Acidification

The outer membranes of Gram-negative bacteria and mitochondria contain proteins with a distinct β-barrel tertiary structure that could function as a molecular pattern recognized by the innate immune system. Here, we report that purified outer membrane proteins (OMPs) from different bacterial and mitochondrial sources triggered the induction of autophagy-related endosomal acidification, LC3B lipidation, and p62 degradation. Furthermore, OMPs reduced the phosphorylation and therefore activation of the multiprotein complex mTORC2 and its substrate Akt in macrophages and epithelial cells. The cell surface receptor SlamF8 and the DNA-protein kinase subunit XRCC6 were required for these OMP-specific responses in macrophages and epithelial cells, respectively. The addition of OMPs to mouse bone marrow–derived macrophages infected withSalmonellaTyphimurium facilitated bacterial clearance. These data identify a specific cellular response mediated by bacterial and mitochondrial OMPs that can alter inflammatory responses and influence the killing of pathogens.

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