The antibacterial activity of Ga3+ is influenced by Llgand complexation as well as the bacterial carbon source
2011 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 55, no 12, 5568-5580 p.Article in journal (Refereed) Published
Gallium ions have previously been shown to exhibit antibacterial and antibiofilm properties. In this study we report differential bactericidal activity of two gallium complexes; gallium desferrioxamine B (Ga-DFOB) and gallium citrate (Ga-cit). Modeling of gallium speciation in growth medium showed that DFOB and citrate both can prevent precipitation of Ga(OH)(3), but some precipitation can occur above pH 7 with citrate. Despite this, Ga-cit inhibitory concentrations (IC(90)) were lower than those of Ga-DFOB for clinical isolates of Pseudomonas aeruginosa, and several reference strains of other bacterial species. Treatment with Ga compounds mitigated damage inflicted on murine J774 macrophage-like cells infected with P. aeruginosa PAO1. Again, Ga-cit showed more potent mitigation than did Ga-DFOB. Ga was also taken up more efficiently by P. aeruginosa in the form of Ga-cit than in the form of Ga-DFOB. Neither Ga-cit nor Ga-DFOB was toxic to several human cell lines tested and no pro-inflammatory activity was detected in human lung epithelial cells after exposure in vitro. Metabolomic analysis was used to delineate the effects of Ga-cit on the bacterial cell. Exposure to Ga resulted in lower concentrations of glutamate, a key metabolite for P. aeruginosa, and of many amino acids, indicating that Ga affects various biosynthesis pathways. Altered protein expression profile in presence of Ga-cit suggested that some compensatory mechanisms were activated in the bacterium. Furthermore, the antibacterial effect of Ga was shown to vary depending on the carbon source, which has importance in the context of medical applications of gallium.
Place, publisher, year, edition, pages
Washington, D. C.: American Society for Microbiology , 2011. Vol. 55, no 12, 5568-5580 p.
IdentifiersURN: urn:nbn:se:umu:diva-49039DOI: 10.1128/AAC.00386-11PubMedID: 21947396OAI: oai:DiVA.org:umu-49039DiVA: diva2:452833