Galacto-oligosaccharides as an anti-bacterial and anti-invasive agent in lung infections. (April 2022)

• Record Type: Journal Article
• Authors: Cai, Yang; van Putten, Jos P.M.; Gilbert, Myrthe S.; Gerrits, Walter J.J.; Folkerts, Gert; Braber, Saskia
• Is Part Of: Biomaterials. Volume 283(2022)
• Publication Date: 2022-04
• Subjects: Carbohydrate-based biomaterials -- Airway inflammation -- Intranasal drug delivery -- Bactericidal effect -- Antibiotic adjuvant -- Respiratory pathogens; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2022.121461
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Emerging antimicrobial resistance in infections asks for novel intervention strategies. Galacto-oligosaccharides (GOS) might be attractive alternatives to antibiotics due to their anti-inflammatory and anti-adhesive properties. Mannheimia haemolytica is one of the major Pasteurellaceae associated with bovine lung infections. Using M. haemolytica, we demonstrated that GOS have the capacity to reduce bacterial viability and can be used as adjuvant to improve antibiotic efficacy. Using M. haemolytica -treated primary bronchial epithelial cells (PBECs) of calves, we identified the anti-adhesive and anti-invasive activities of GOS. The observed inhibition of cytokine/chemokine release and the prevention of airway epithelial barrier dysfunction in M. haemolytica -treated PBECs by GOS might be related to the downregulation of "toll-like receptor 4/nuclear factor-κB" pathway and the anti-invasive and anti-adhesive properties of GOS. Particularly, GOS lowered lipopolysaccharides- but not flagellin-induced cytokine/chemokine release in calf and human airway epithelial cells. Finally, we performed in vivo experiments in calves and demonstrated for the first time that intranasal application of GOS can relieve lung infections/inflammation and lower M. haemolytica positivity in the lungs without affecting clinical performance. These findings not only shed light on the anti-inflammatory mechanisms of GOS during lung infections, but GOS might also be a promising anti-bacterial agent for preventing (lung) infections. Graphical abstract: Image 1