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A DFT study of the gallium ion-binding capacity of mature Pseudomonas aeruginosa biofilm extracellular polysaccharide

Intravenous gallium therapy is a non-antibiotic approach to limit Pseudomonas aeruginosa biofilm proliferation, by outcompeting iron for siderophore binding. Gallium therapy represents a viable therapeutic strategy for cystic fibrosis (CF) patients harbouring mucoid P. aeruginosa biofilm lung infect...

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Detalles Bibliográficos
Autores principales: Hills, Oliver J., Poskrobko, Zuzanna, Scott, Andrew J., Smith, James, Chappell, Helen F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266685/
https://www.ncbi.nlm.nih.gov/pubmed/37315081
http://dx.doi.org/10.1371/journal.pone.0287191
Descripción
Sumario:Intravenous gallium therapy is a non-antibiotic approach to limit Pseudomonas aeruginosa biofilm proliferation, by outcompeting iron for siderophore binding. Gallium therapy represents a viable therapeutic strategy for cystic fibrosis (CF) patients harbouring mucoid P. aeruginosa biofilm lung infections. Siderophore deficient P. aeruginosa isolates still demonstrate a hindered biofilm proliferation when exposed to gallium but it is currently unknown whether exogenous gallium has any disruptive influence on the exopolysaccharide (EPS), the major mucoid P. aeruginosa CF lung biofilm matrix component. To that end, Density-Functional Theory (DFT) was deployed to assess whether gallium (Ga(3+)) could be substituted into the mature mucoid EPS scaffold in preference of calcium (Ca(2+))—the native EPS cross-linking ion. Removal of the stable, bound native calcium ions offers a large enthalpic barrier to the substitution and the mature EPS fails to accommodate exogenous gallium. This suggests that gallium, perhaps, is utilising a novel, possibly unknown, ferric uptake system to gain entry to siderophore deficient cells.