Atividade antibacteriana de nitrato de gálio frente à isolados de Klebsiella pneumoniae resistentes à polimixina B

Abstract

Assumed the importance of iron in bacterial physiology and pathogenicity, 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 repurposed as an antimicrobial drug. Ga (III) disrupts ferric iron-dependent metabolic pathways, thereby inhibiting microbial growth. In this study we found that gallium nitrate III (GaN), inhibits the growth of a collection of 20 polymyxin resistant Klebsiella pneumoniae strains at concentrations ranging from 2 to 16µg/mL, using RPMI-HS, in which the low iron content and the presence of human serum better mimic the in vivo environment. GaN also protected Caenorhabditis elegans from polymyxin-resistant K. pneumoniae strains lethal infection, with survival rates of >75%. GaN also showed synergism with polymyxin B, suggesting that a polymyxin B-GaN combination holds promise as a last-resort therapy for infections caused by resistant polymyxin B K. pneumoniae strains.