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Publication Abstract from PubMed

The Burkholderia cepacia complex (Bcc) is a group of Gram-negative opportunistic pathogens causing infections in people with cystic fibrosis (CF). Bcc is highly antibiotic resistant, making conventional antibiotic treatment problematic. The identification of novel targets for anti-virulence therapies should improve therapeutic options for infected CF patients. We previously identified that the peptidoglycan-associated lipoprotein (Pal) was immunogenic in Bcc infected CF patients; however, its role in Bcc pathogenesis is unknown. The virulence of a pal deletion mutant (Deltapal) in Galleria mellonella was 88-fold reduced (p < .001) compared to wild type. The lipopolysaccharide profiles of wild type and Deltapal were identical, indicating no involvement of Pal in O-antigen transport. However, Deltapal was more susceptible to polymyxin B. Structural elucidation by X-ray crystallography and calorimetry demonstrated that Pal binds peptidoglycan fragments. Deltapal showed a 1.5-fold reduced stimulation of IL-8 in CF epithelial cells relative to wild type (p < .001), demonstrating that Pal is a significant driver of inflammation. The Deltapal mutant had reduced binding to CFBE41o(-) cells, but adhesion of Pal-expressing recombinant E. coli to CFBE41o(-) cells was enhanced compared to wild-type E. coli (p < .0001), confirming that Pal plays a direct role in host cell attachment. Overall, Bcc Pal mediates host cell attachment and stimulation of cytokine secretion, contributing to Bcc pathogenesis.

The Burkholderia cenocepacia peptidoglycan-associated lipoprotein is involved in epithelial cell attachment and elicitation of inflammation.,Dennehy R, Romano M, Ruggiero A, Mohamed YF, Dignam SL, Mujica Troncoso C, Callaghan M, Valvano MA, Berisio R, McClean S Cell Microbiol. 2017 May;19(5). doi: 10.1111/cmi.12691. Epub 2016 Nov 25. PMID:27886433^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.