Document Type

Article

Rights

Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence

Disciplines

3. MEDICAL AND HEALTH SCIENCES

Abstract

Burkholderia cepacia complex (Bcc) causes chronic opportunistic lung infections in people with cystic fibrosis (CF) resulting in a gradual lung function decline and, ultimately, patient death. Bcc is a complex of eighteen species and is rarely eradicated once a patient is colonised, therefore vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in attachment of Bcc to lung epithelial cells. Fourteen proteins were reproducibly identified by 2-DE from four Bcc strains, representative of two Bcc species: B. cenocepacia, the most virulent and B. 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 previously published data on these proteins in other species. The E. coli strains expressing recombinant Linocin and OmpW showed enhanced attachment (4.2- and 3.9-fold) to lung cells, compared to control, confirming that both proteins are involved in host cell attachment. Immunoproteomic analysis using serum from Bcc colonised CF patients confirmed that both proteins elicit potent humoral responses in vivo. Mice immunised with either recombinant Linocin or OmpW were protected from B. cenocepacia and B. multivorans challenge. 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 multi-subunit vaccine. Furthermore, it highlights the potential of our proteomics approach to identify potent antigens against other difficult pathogens.

DOI

https://doi.org/10.1128/IAI.01248-15

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