Antibacterial activity of gallium nitrate against polymyxin-resistant Klebsiella pneumoniae strains

Iron uptake and metabolism have become attractive targets for the development of new antibacterial drugs. In this scenario, the FDA-approved iron mimetic metal gallium [Ga (III)] has been successfully researched as an antimicrobial drug. Ga (III) inhibits microbial growth by disrupting ferric iron-dependent metabolic pathways. In this study, we revealed that gallium nitrate III (GaN) inhibits the growth of a collection of twenty polymyxin-resistant Klebsiella pneumoniae strains at concentrations ranging from 2 to 16µg/mL, using a medium, on which the low iron content and the presence of human serum better mimic the in vivo environment. GaN was also successful in protecting Caenorhabditis elegans from polymyxin-resistant K. pneumoniae strains lethal infection, with survival rates of >75%. GaN also exhibited synergism with polymyxin B, suggesting that a polymyxin B-GaN combination holds promise like as one alternative therapy for infections caused by resistant polymyxin B K. pneumoniae strains.