Golden Adjuvant
Infections caused by multidrug-resistant bacteria are generating increasing public health concerns around the world. A World Health Organization report last year said that antibiotic resistance was rising to dangerously high levels in all parts of the world, and called for increased investment to address the problem.
For several years, researchers have recognized the antimicrobial properties of specially adapted gold nanoparticles, but it was difficult to deliver them to the site of bacterial inflammation without harming healthy cells. A new study by an international team of scientists from the University of Leeds (UK), Southern University of Science and Technology (Shenzhen, China) and Fudan University (Shanghai, China) has developed a way to package gold nanoclusters in a double molecular shell, which makes them less toxic to healthy tissues without reducing antibacterial properties. In vitro laboratory studies of this approach have shown high efficiency in terms of the destruction of a number of bacteria, including pathogens of nosocomial infections resistant to standard methods of antibacterial treatment.
The principle of the method
The strategy is based on the physical property of opposite charges to attract. Knowing that bacterial cell walls are more strongly negatively charged than mammalian cells, and considering the ability of opposite charges to attract, the researchers placed gold nanoclusters in positively charged molecules, or ligands. Following the law of electrostatics, it delivers nanoclusters only to the walls of bacterial cells, which they destroy. Damage to the cell membrane increases the permeability of the bacterial cell to standard antibiotics, including those that are weak or ineffective against resistant bacteria.
This strategy, however, has one drawback: the positively charged shell of nanoclusters is also toxic to healthy mammalian host cells.
To protect healthy cells, the scientists added a second ligand to the shell around each nanocluster. These molecules have both positive and negative charges and are called zwitter ions, they are also found in the lipids of mammalian cell membranes. This makes gold nanoclusters more compatible with host cells and facilitates their passage through the kidneys and excretion from the body.
Gold nanocluster in a double molecular shell. Blue ligands are zwitter-ion, red ligands are positively charged. They are bound to the Au25 (brown) cluster by thiol (yellow) molecules. Source: University of Leeds.
During laboratory tests, scientists tested whether gold nanoclusters would be effective in reducing the resistance of bacterial cells to antibiotics. They used several strains of gram-positive bacteria, including methicillin-resistant epidermal staphylococcus (MRSE), which is the causative agent of some nosocomial infections. Three antibiotics from different pharmacological groups were tested in combination with and without gold nanoclusters.
In cases where the antibiotic was used in combination with nanoclusters, an improved antimicrobial effect was observed: one of the antibiotics suppressed the growth of MRSE at a concentration 128 times lower than the standard dosage.
Thus, the researchers showed a way to use gold nanoclusters as a mechanism to increase the effectiveness of antibiotics, which have lost relevance due to the persistent resistance of bacteria to them. They hope that the results of the research will be used by the pharmaceutical industry, because mixing gold nanoclusters with existing antibiotics can be a faster and cheaper alternative to developing many new antibiotics in response to the resistance of bacteria to old ones.
Article Z.Pang et al. Controlling the pyridinium–zwitterionic ligand ratio on atomically precise gold nanoclusters allowing for eradicating Gram-positive drug-resistant bacteria and retaining biocompatibility is published in the journal Chemical Science.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Leeds: Going for gold to reduce antibiotic resistance.