Antibacterial effects of gold-chitosan nanocomposites on human macrophages infected by intracellular pathogenic bacteria

Introduction: Bacteria have developed resistances to antibiotics with the subsequent negative consequences in the treatment of different pathogenic infections. Nanomaterials have emerged as a potential bactericidal approach to... [ view full abstract ]

Introduction: Bacteria have developed resistances to antibiotics with the subsequent negative consequences in the treatment of different pathogenic infections. Nanomaterials have emerged as a potential bactericidal approach to avoid multidrug resistances. We previously demonstrated that gold-chitosan nanocomposites show bactericidal but not cytotoxic action at the doses tested (Regiel-Futyra et al., 2015). Here, we evaluated their action in a co-culture model of macrophages infected by different bacteria to closely mimic a real infection scenario.
Methods: Nanocomposites were prepared by a solvent evaporation method by using chitosan with medium average molecular weight and chitosan based gold nanoparticles dispersions with two different initial gold precursor concentrations, 1 and 2 mM. Then, gold nanoparticles and chitosan-gold nanocomposites were characterized by UV-Vis spectroscopy, transmission electron microscopy and Fourier Transform Infrared Spectra analysis. Cytotoxic effects on different cell lines and bacteria were evaluated separately (Regiel-Futyra et al., 2015). Cytotoxic effects of gold chitosan nanocomposites on macrophages infected with Gram positive (Staphylococcus aureus) and Gram negative bacteria (Escherichia coli) were evaluated and the antimicrobial activity was studied by the colony-forming unit assay.
Results: Gold chitosan nanocomposites exhibited potent antibacterial effects at the subcytotoxic concentrations assayed in both infection macrophage models being more accentuated in the Gram positive bacteria model in which one of our experimental groups exerted a complete bactericidal effect obtaining no bacteria colonies after treatment of the infected macrophages with the gold-chitosan based nanocomposites.
Discussion: The development of novel bactericidal strategies is imperative regarding the high prevalence of multidrug resistances arising in bacteria. By 2050 antimicrobial resistance would lead to 10 million people deaths every year and a reduction of 2% to 3.5% in Gross Domestic Product. Our study showed that at non cytotoxic concentrations, gold chitosan nanocomposites were able to kill both Gram positive and Gram negative bacteria in infection models in vitro without damaging host cells and avoiding the well-known cyto- and genotoxic effects of other metal nanomaterials such as silver and copper nanoparticles. This approach represents a potential basis in the design and development of bactericidal materials to efficiently halt the progression of bacteria colonization avoiding the growing problem of multidrug resistances.