They turned manganese, a trace element essential for the human body, into an effective antibiotic by anchoring it in the structure of chemically modified graphene using atomic engineering. Tests in animal models have shown that the new material has great potential, particularly in local therapies such as wound healing. The discovery was published in the prestigious journal Advanced Materials and the scientists have filed a European patent to protect the material.
“The developed material can kill and inhibit the growth of all types of bacteria we have studied, including highly resistant pathogens. It works at low concentrations at which it is completely harmless to human cells. Bacteria are unable to develop resistance to it, which is one of the biggest problems in modern medicine. All of these results are excellent prerequisites for the use of atomic antibiotics in practice,” said Radek Zbořil, a physical chemist and author of the research concept, who works at the Centre for Energy and Environmental Technologies (CEET) at VŠB-TUO and CATRIN UP. In addition to experts from the CEET Nanotechnology Centre, scientists from the national supercomputing centre IT4Innovations also participated in the research, and the work was supported by the REFRESH project.
Frontal attack of manganese
In developing the antibiotic, the scientists have capitalised on their expertise in graphene chemistry and atomic engineering, which they have been working on extensively in recent years. This time, they have relied on a graphene derivative enriched with oxygen and nitrogen atoms, chemically incorporating manganese – a transition metal that is involved in the human body in metabolism, bone formation, blood sugar regulation and protection of cells from oxidative stress.
“We decided to attack not the weakest but one of the strongest points of bacteria – the carbohydrates in their cell wall and cell membrane, which are crucial for bacterial survival. Among other things, they have a protective function, mediate the transfer of substances and communication with the environment, and serve as energy reserves for the bacteria. By chemically binding manganese to selected groups of carbohydrates, their main functions were suppressed and cell death ensued. The role of the graphene carrier is crucial, as it ensures the transfer of manganese ions to the surface of the bacteria and enables their frontal chemical attack on the carbohydrate molecules,” Zbořil explained the new approach.
It acts even on the most resistant bacteria
The new material is also effective against bacteria for which existing antibiotics are not sufficient. “We have demonstrated an excellent bactericidal effect against all bacteria from the so-called ESCAPE group, which includes highly resistant bacterial pathogens. These bacteria are particularly dangerous because they resist conventional antibiotics, which complicates treatment and increases the risk of serious infections, especially in hospital settings. The nuclear antibiotic was the only one effective against all resistant bacteria compared to commercial antibiotics,” explained the first author of the paper, David Panáček from CATRIN UP and CEET VŠB-TUO.
The researchers verified the effect of the atomic antibiotic not only in laboratory conditions, but also in mouse models in collaboration with colleagues from China. “In in-vivo tests, there was a very fast and effective healing of skin infection caused by a resistant strain of Staphylococcus aureus (golden staphylococcus) and a dramatic decrease in all inflammatory markers. Thus, we can already consider the use of a new type of antibiotic for wound coverage or antibacterial treatment of surfaces of artificial materials. Here we see a huge potential in terms of the possibility of suppressing the formation of bacterial coatings on, for example, artificial joint replacements, stents or cannulas. Thanks to its mechanism of action, the new material could also prevent the development of complicating infections, which would have a major impact on healthcare,” said Milan Kolář, a microbiologist and dean of the Faculty of Medicine at UP, who was significantly involved in the research.
Atomic antibiotic opens up new possibilities
The scientific team will continue the research and test the material for systemic antibiotic treatment. “Existing antibiotics can no longer treat some serious infections and bacterial sepsis is an increasingly common cause of death. Therefore, we want to test the potential of atomic antibiotics to treat the most serious bacterial diseases,” Kolář added.
According to the UN, it is estimated that if bacterial resistance continues to increase at the same rate as now, untreatable infections caused by multidrug-resistant bacteria will be the leading cause of death by 2050. So-called ‘superbugs’ thus pose a global threat to humanity, the solution to which lies in the development of new antibacterial agents capable of bypassing the existing mechanisms that bacteria develop to protect themselves. The research of the scientific team, which also included colleagues from the Faculty of Science of UP and two Chinese institutions, thus confirms the unsuspected potential of atomic engineering in solving one of the greatest scientific and social challenges.
Source.
Press release: ‘Atomic antibiotics developed by Czech scientists can counter bacterial resistance’ [online]. 3 October 2023. Available from: https://www.vsb.cz/cs/detail-novinky/?reportId=47998&linkBack=%2Fcs%2Findex.html
