Pathogenic and opportunistic bacteria rapidly develop resistance to antibiotics and it is likely that the next following pandemic after COVID-19 will be bacterial in origin. Inorganic nanoparticles offer one, albeit insufficiently explored, avenue for developing alternatives to the shortcomings of traditional, small-molecule antibiotics, which include resistance, complex preparation protocols, high cost, and others. Cheap and simple to make, calcium phosphate (CP) belongs to the new wave of abundant and naturally accessible nanomaterials applicable as a means to various technological ends. Here I will present findings on our comprehensive study on the intrinsic antibacterial effect exhibited by two distinct CP phases: an amorphous CP (ACP) and hydroxyapatite (HAp). The effect is prominent against a number of regular bacterial species, including <i>S. aureus, S. epidermis, E. faecalis, E. coli</i> and <i>P. aeruginosa</i>, but also their multidrug-resistant (MDR) analogues. Interestingly, ACP proves to be more effective against Gram-positive species, with respect to which HAp is mostly inert, yet this trend becomes reversed for the MDR strains. In addition to the intrinsic antimicrobial effect of CP nanoparticles, we have also observed a synergistic effect between the nanoparticles and certain antibiotics. Both forms of CP engage in a synergistic relationship with a variety of concomitantly delivered antibiotics, and enable even antibiotics completely ineffective against particular bacterial strains to significantly suppress their growth. These findings present grounds for the further optimization of CP nanoparticle properties for activity against regular and MDR bacterial strains, while retaining the superb safety profile and positive eukaryotic vs. prokaryotic cell selectivity that is characteristic of this material. In addition to these efficacy studies, results of studies aimed at elucidating the mechanism of action of CP nanoparticles will be presented. Here, I will demonstrate that proper understanding of the mechanism of action is an interfacial issue in need of juxtaposition of the physicochemical properties of nanoparticles and the fine molecular effects on their targets in the bacterial cell.

Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials

ACS Spring Meeting 2021

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