Identification by Reverse Vaccinology of Three Virulence Factors in Burkholderia cenocepacia That May Represent Ideal Vaccine Antigens

The Burkholderia cepacia complex comprises environmental and clinical Gram-negative bacteria that infect particularly debilitated people, such as those with cystic fibrosis. Their high level of antibiotic resistance makes empirical treatments often ineffective, increasing the risk of worst outcomes and the diffusion of multi-drug resistance. However, the discovery of new antibiotics is not trivial, so an alternative can be the use of vaccination. Here, the reverse vaccinology approach has been used to identify antigen candidates, obtaining a short-list of 24 proteins. The localization and different aspects of virulence were investigated for three of them-BCAL1524, BCAM0949, and BCAS0335. The three antigens were localized in the outer membrane vesicles confirming that they are surface exposed. We showed that BCAL1524, a collagen-like protein, promotes bacteria auto-aggregation and plays an important role in virulence, in the Galleria mellonella model. BCAM0949, an extracellular lipase, mediates piperacillin resistance, biofilm formation in Luria Bertani and artificial sputum medium, rhamnolipid production, and swimming motility; its predicted lipolytic activity was also experimentally confirmed. BCAS0335, a trimeric adhesin, promotes minocycline resistance, biofilm organization in LB, and virulence in G. mellonella. Their important role in virulence necessitates further investigations to shed light on the usefulness of these proteins as antigen candidates.

Automated summary

The Burkholderia cepacia complex is a group of Gram-negative bacteria that infects people with weakened immune systems, such as those with cystic fibrosis. Due to their high level of antibiotic resistance, commonly used treatments are often ineffective, leading to worse outcomes and the spread of multi-drug resistance. In this study, reverse vaccinology was used to identify potential antigens for vaccination. Three proteins (BCAL1524, BCAM0949, and BCAS0335) were investigated for their localization and virulence-related properties. The findings suggest that these proteins play important roles in the virulence of Burkholderia cepacia complex and further research is needed to assess their potential as antigen candidates.