Bacterial resistance to silver nanoparticles can be overcome

A mechanism that allows bacteria to resist the antibacterial effects of silver nanoparticles was discovered by scientists from the Regional Centre of Advanced Technologies and Materials (RCPTM) together with colleagues from the Faculty of Medicine and Dentistry of Palacký University and the Centre of the Region Haná. The scientists also developed a way to overcome this resistance mechanism. This remarkable achievement, which could play a significant role in resolving the global antibiotics resistance crisis, made the front page of Nature Nanotechnology in January 2018. This was the first time a team consisting solely of Czech scientists had published its results in this journal, which is arguably the most prestigious international journal of nanotechnology.

Scientists from Olomouc have been studying the biological effects of noble metal nanoparticles for twenty years. Details of their effects on diverse bacteria, including highly resistant phyla, were reported in 2006 (Panáček A. et al. J. OF Physical Chem. B 110,  16248-16253, 2006), sparking intense academic and commercial interest in the applications of nanosilver. The increasing use of silver nanoparticles in commercial products prompted the team at Olomouc to consider the possible emergence of bacterial resistance induced by repeated exposure to nanosilver, which could weaken or eliminate its antibacterial activity. Bacteria have already developed resistance to several antibiotics, reducing their medical usefulness. After five years of study, the team discovered that bacteria can indeed develop resistance to nanosilver, but it can be easily overcome.

‘It is already well-known that silver nanoparticles lose their antimicrobial effect if they form larger particles called aggregates. We found that flagellated bacteria can attack this weak point of silver nanoparticles. Repeated exposure to nanosilver causes some bacteria to secrete a protein called flagellin, which is a component of the flagella. This protein weakens the repulsive forces between the silver particles and acts as a glue, making them cluster into aggregates and thus lose their antibacterial properties,’ said Aleš Panáček, lead author of the study.

This resistance could be overcome by adding substances that inhibit the production and release of flagellin. Such substances can be found in pomegranate extracts. ‘If a pomegranate extract is applied along with silver nanoparticles, the bacteria will fail to produce flagellin, destroying their resistance to the silver nanoparticles,’ said Libor Kvítek, a pioneer of nanosilver research at Olomouc.

Olomouc scientists have also developed a technology (which has been patented in Europe and the USA) that circumvents this resistance mechanism by forming strong chemical bonds between nanoparticles and various materials including plastics, metals, and fabrics. Immobilizing the nanoparticles like this prevents their aggregation, disabling the flagellin-based resistance mechanism and preventing the formation of bacterial films on the treated material. A couple of businesses in Europe have already expressed interest in this technology. ‘This is the right course of action because robust nanosilver binding will prevent nanoparticle aggregation and eliminate bacterial resistance based on flagellin. At the same time, the nanoparticles will be not released into the environment and non-bacterial organisms will not be exposed to them,’ explained Radek Zbořil, RCPTM Director.

The scientists from Olomouc have already published several studies in which they explored the high activity of silver nanoparticles against yeasts and the possibility of restoring the activity of antibiotics against multidrug-resistant bacteria by applying them in conjunction with nanosilver at very low concentrations that are non-toxic to mammalian cells.