Open AccessThe Antibacterial Activity of Ga 3+ Is Influenced by Ligand Complexation as Well as the Bacterial Carbon Source
Author(s) -
Olena Rzhepishevska,
Barbro EkstrandHammarström,
Maximilian W. Popp,
Erik Björn,
Anders Bucht,
Anders Sjöstedt,
Henrik Antti,
Madeleine Ramstedt
Publication year - 2011
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00386-11
Subject(s) - gallium , bacteria , pseudomonas aeruginosa , ligand (biochemistry) , antibacterial activity , chemistry , metabolite , microbiology and biotechnology , bacterial growth , in vitro , minimum inhibitory concentration , pseudomonadaceae , amino acid , biochemistry , nuclear chemistry , biology , receptor , organic chemistry , genetics
Gallium ions have previously been shown to exhibit antibacterial and antibiofilm properties. In this study, we report differential bactericidal activities 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 90% inhibitory concentrations (IC90 ) were lower than those of Ga-DFOB for clinical isolates ofPseudomonas aeruginosa and several reference strains of other bacterial species. Treatment with Ga compounds mitigated damage inflicted on murine J774 macrophage-like cells infected withP. aeruginosa PAO1. Again, Ga-Cit showed more potent mitigation than did Ga-DFOB. Ga was also taken up more efficiently byP. 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 proinflammatory activity was detected in human lung epithelial cells after exposurein 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 forP. aeruginosa , and of many amino acids, indicating that Ga affects various biosynthesis pathways. An altered protein expression profile in the 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.