Antibiotic-resistant bacteria were responsible for nearly 5 million deaths globally in 2019, as detailed in The Lancet. The rise and fall of antibiotics is a topic that is deeply personal to Dr. Ana Santos, who led the EU-funded project REBELLION.
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Six types of resistant bacteria do the greatest damage. According to the World Health Organization, drug-resistant diseases might directly cause 10 million deaths by 2050.
My family members were dying of infections. I started to realize that we are going back in time – our antibiotics are no longer effective.
Dr. Ana Santos, REBELLION
Santos has been involved in the effort to decrease such worrying figures: she supervised a research project that got EU money to build tiny robots capable of killing resistant bacteria. The project, named REBELLION, lasted 39 months until April 2023.
Santos added, “I came across this concept of molecular machines that drill into cells. We have to start thinking outside the box.”
Scottish physician Alexander Fleming is credited with discovering penicillin, the first real antibiotic, in 1928. Penicillin is produced by a specific kind of mold. Millions of lives were saved as more antibiotics, frequently produced by soil bacteria, were discovered.
However, bacteria developed a variety of defense mechanisms to withstand antibiotics in what amounted to an arms competition.
Bacteria Borders
Santos was researching how bacteria survive and perish in malnutrition when her two relatives and a friend passed away from diseases. So, she decided to shift the emphasis of her studies.
“I was feeling frustrated because I was seeing this urgent problem and I was not doing anything about it. People are increasingly dying of infections that are resistant to antibiotics,” Santos stated.
She asked for assistance from specialists in this field and collaborated with a team in Spain to investigate the mechanism by which minuscule molecular devices spear microorganisms. The devices are made up of two molecules joined by a chemical connection; when light strikes, the top part of the molecule spins quickly like a drill.
Similar to how a key fits into a lock, antibiotics frequently cling to a particular bacterial protein. The problem lies in the fact that germs have the ability to alter physically, rendering the key inoperable in the lock. Antibiotics are not kept inside.
The theory behind the nanomachines is that germs would find it more difficult to get past them.
These bug-killing devices were introduced by Santos as part of REBELLION.
Superbug Killer
They are essentially minnows alongside larger bacteria since their two halves are less than 100 nanometers, or one thousandth the diameter of a human hair.
In her lab, Santos released a vast number of her nanomachines into bacterial clumps. When the bacteria were exposed to light, the machines attached themselves to them and started drilling and spinning.
Santos was ecstatic to see, under her microscope, bacterium cells covered with small holes.
Subsequent tests revealed that a variety of strains that often infect humans could have been killed by tiny drills.
She then took a different approach, using less equipment to combat the deadly superbug known as methicillin-resistant Staphylococcus aureus, or MRSA, which is particularly prevalent in hospitals. The likelihood of harming human cells would be reduced with a smaller concentration of machines.
The MRSA was sufficiently penetrated by the devices to make it susceptible to antibiotics once more.
Santos further added, “It is very hard for bacteria to develop resistance against this action. It’s like dropping bombs on them.”
Wounds Healer
The researchers must make sure the nanomachines are safe to employ on people before deploying this new weapon against resistant bacteria. Ensuring that germs are targeted instead of human cells is necessary.
The positively charged nature of the nanomachines is one early cause for hope. Consequently, they choose to attach themselves to negatively charged bacteria as opposed to more neutral human cells.
When Santos introduced the nanomachines into worms, there was no negative effect observed. Aiming to bring this approach closer to patients, she is getting ready for the next phase, which involves safety testing on mice.
If it is successful, patients with wound infections, particularly those with severe burns who are more vulnerable to infection, may receive treatment first.
The nanomachines might be applied topically and turned on by light to pierce the bacteria causing the wound.
Top European Team
Nanomachines have been in the spotlight before.
For creating nanomachines with molecular motors that could be activated by UV light, Professor Ben Feringa of the University of Groningen in the Netherlands was awarded the Nobel Prize in Chemistry in 2016.
When exposed to light, the molecules undergo a form shift that makes them useful as switches or triggers. Feringa even created a single-molecule nanocar that could operate on a copper surface.
He assists in overseeing a research initiative sponsored by the EU that teaches aspiring scientists about molecular machines. The four-and-a-half-year initiative, called BIOMOLMACS, will end in June 2024.
Although they have not made it to hospitals yet, scientists and physicians are excited about the possibility of using nanomachines to cure cancer patients. The side effects associated with several cancer treatments on the market today include hair loss, nausea, exhaustion, and weakened immune systems. This is because healthy bystander cells can get damaged by the drugs.
In the future, it could be possible for nanomachines to burrow within any tumor and administer drugs that destroy cancer cells directly to a patient’s cancer.
BIOMOLMACS supervisor Professor Maria Vicent of the Valencia Biomedical Research Foundation in Spain creates tiny carriers that transport drugs to breast cancer cells.
Professor Jan van Hest from Eindhoven University of Technology in the Netherlands is another supervisor. He creates materials that can be utilized to transport vaccinations or nanomedicines within cells, particularly cancer cells.
Other distinguished experts from around Europe have contributed their expertise to Van Hest, Vicent, and Feringa.
Polymer nanoparticles are being developed by Professor Remzi Becer of the University of Warwick in the United Kingdom to deliver gene therapies to specific places within patients in the future. Since the particles can function as a key to open cells in the body, they are frequently coated sugars.
These synthetic sugars can interact with cell membranes and can give the particle a key to open the door and get a gene inside the cell.
Remzi Becer, Professor, University of Warwick
Becer oversees the project with fifteen doctorate candidates and mentors two scientists in their early careers.
Lipid nanoparticles, or small spheres formed of lipids that can get into cells without harm, are the subject of research by Professor Robin Shattock of Imperial College London, located in the UK. To develop COVID-19 vaccinations, lipid nanoparticles were the real breakthrough.
Emerging Talent
These elite European researchers could be teaching the next generation of medical professionals.
Becer added, “The next big change for the pharma industry will be to train our genes to prevent cancer or to fight against cancer.”
According to him, BIOMOLMACS could prepare scientists for positions at some of the companies that are creating nanomachines to deliver these types of biological drugs to certain organs.
Meanwhile, REBELLION’s Santos hopes that her findings can help cancer patients, whose treatments often leave them vulnerable to bacterial infections.
Santos concluded, “My good friend had beaten cancer but then she died of an infection. I remember when the doctor said: “the bacteria is resistant to everything – there’s nothing we can do.”
She intends to make sure that physicians never have to say anything like this.
The EU provided funding for the research in this article through the Marie Skłodowska-Curie Actions (MSCA).
Journal Reference:
Antimicrobial Resistance Collaborators (2023) Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. doi:10.1016/S0140-6736(21)02724-0.
Source: https://projects.research-and-innovation.ec.europa.eu/horizon-magazine