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František Štěpánek

František Štěpánek

Member of the Scientific council of Chemistry

Professor František Štěpánek, Ph.D. was born in 1974. He studied at the University of Chemistry and Technology in Prague and earned his Ph.D. at Pierre and Marie Curie University in Paris. After his studies he worked as a researcher at Unilever R&D in the United Kingdom and later lectured as a visiting professor at Imperial College London. Since 2008 he has been at the Department of Chemical Engineering of the University of Chemistry and Technology in Prague. He works on the synthesis and characterisation of functional micro- and nanoparticles, and studies the remote control of enzymatic reactions and the controlled release of active substances.

Pneumonia, scarlet fever or a middle ear infection — illnesses doctors handle routinely today thanks to antibiotics. In the future they may threaten life again, returning humankind to the era before penicillin. František Štěpánek, however, is opening a new era of natural antibiotics to which no resistance develops.

Antibiotics are not prescribed only to people today; they are also given preventively to cattle, for instance, so we consume them indirectly through milk and meat. In various forms they then persist in the environment for years. Bacteria meet them more and more often, adapt, and become resistant to them. We already know resistant bacterial strains for which no effective drug exists.

Professor Štěpánek's research group uses allicin — a substance obtainable from ordinary garlic — to suppress and destroy bacteria. Allicin is produced when garlic cells are damaged, through a reaction between the enzyme alliinase and alliin molecules, and it has a powerful antibiotic effect. But only for a few hours. That instability is in fact highly desirable, because the bacteria do not have time to adapt. Until now the problem was how to get allicin to the site of infection in time.

The innovation in Professor Štěpánek's method lies in isolating the components of allicin and transporting them efficiently through the human body to the site of infection. Alliinase and alliin are placed into miniature carriers made of fats and sugars, and the mixture of carriers is put into an ordinary tablet, which dissolves in the body; on contact with water the shells become permeable. Their opposite charges draw the substances together and they begin to react directly inside our body. Allicin, a highly effective antibiotic, is thus created inside the body itself. Unlike traditional antibiotics, though, unstable allicin is present in the human body for only a few hours, and the bacteria that survive its attack do not have enough time to adapt and become resistant to it. This unique method could be used not only against internal infections but also to treat skin and vaginal infections. A patent application, currently under negotiation, should make its application and commercial use possible. A new era of natural antibiotics to which no resistance develops may be opening.

Listen: Garlic, the future weapon against bacteria (in Czech)

Garlic, the future weapon against bacteria

Infectious diseases resist common antibiotics ever more effectively. According to an analysis by the World Economic Forum (Global Risks Report 2013), the resistance of dangerous microorganisms is considered one of the gravest threats to humankind. A new weapon against resistant bacteria is being prepared by Professor František Štěpánek of the University of Chemistry and Technology in Prague. In 2013 he received almost one million crowns for his research from the Neuron Endowment Fund. He now takes stock of the results so far.

Professor Štěpánek's weapon is an active substance from garlic called allicin. Under laboratory conditions it can kill up to half of the known population of dangerous bacteria. The garlic extract works better than common antibiotics. How is that possible? The active substances in antibiotics are built from stable molecules, so vanishing quantities of them remain for years in the human body and in the environment. Bacteria get used to these substances and gradually resist antibiotics better and better. Allicin molecules, by contrast, survive in the body for only a few hours. During that time they either kill the bacteria or, to put it in lay terms, fall apart. The microorganisms therefore get no chance to grow accustomed to allicin, nor any time to produce a generation resistant to it.

The battle with bacteria that Professor Štěpánek commands begins by sending out a chemical robot. It is a cluster of molecules made of fat and sugar that travels through the bloodstream to the site affected by infection. Such an area usually has a different chemical environment from healthy tissue. As soon as the substance held on the robot's surface recognises that difference, the destruction of the bacteria itself begins. The robot contains two sets of microparticles. One holds the substrate from which allicin is created by chemical conversion. The other contains the enzyme whose action on the substrate produces allicin. It has to be released in the necessary quantity and at the required rate, which is why the correct ratio of the two types of microparticle is essential. Professor Štěpánek's team managed this after some time and then tested allicin on selected cell cultures. The experiments proved that allicin molecules attach to the surface of the bacteria and, in the form of so-called reactive radicals, react very violently. In such an environment the bacteria feel threatened and commit suicide.

Štěpánek's team also studied the rate at which the microparticles held in the chemical robot are converted into allicin. From this stage of the research the scientists determined how long the active substance can be expected to be present in its active form around the microparticles. They also created a mathematical model that makes it possible to predict that time for concentration ranges other than those studied experimentally.

Together with colleagues from Imperial College London, the Czech scientists measured the sorption properties of both types of microparticle and the rate at which they cluster, both dry and in solution. They presented their findings at an international conference in the United Kingdom. The results of the basic research were published in international journals.

The findings of Štěpánek's team could in time be used above all to treat skin, vaginal and lung infections. Testing and approval will, however, take many years. A patent application that should allow commercial use of the newly developed technology is currently being prepared.

An interview with František Štěpánek

What form does your "army" take?
I will use chemical mini-robots. At the site affected by bacteria and threatened by infection, they release an active substance obtained from garlic.

Why garlic in particular?
This crop contains a substance called allicin. Experiments published in the specialist press around the turn of the millennium demonstrated its ability to treat infectious diseases.

And why not use ginger, for example? That also demonstrably kills bacteria.
Garlic is simply more available in our latitudes. It also mattered that we already have the assays worked out for tracking the efficacy of allicin in cell cultures. For ginger we would have to develop them first.

Which bacteria can allicin destroy?
It has been proven in the laboratory that it can kill half of the known population of microorganisms.

Why is garlic extract more successful against bacteria than antibiotics?
The active substances used in common antibiotics have stable molecules. That means vanishing quantities of these substances remain for years in the human body and in the environment. Bacteria get used to them and resistant strains are gradually selected. Allicin molecules, the substance obtained from garlic, survive in the body for only a few hours. In that time they either kill the bacteria at the site of infection or, in lay terms, fall apart. So the bacteria either do not survive the presence of allicin, or they get no chance to grow accustomed to it and produce a generation resistant to it.

How do the chemical mini-robots work against bacteria?
The mini-robot travels through arteries and veins until the blood carries it to the site affected by infection. Such an area usually has a different chemical environment from healthy tissue. The moment the substance held on the robot's surface recognises that difference, it is the signal to start the reaction that produces allicin. Its molecules attach to the surface of the bacteria and begin to react very violently. Bacteria cannot withstand such an attack. I expect hundreds of millions of chemical mini-robots to be travelling through the bloodstream.

Will they gradually accumulate in the patient's body?
There is no such risk, because the mini-robots are assembled from fats and sugars, which the human body can break down into simple substances and consume.

What illnesses will the mini-robots be used to treat?
Skin, vaginal and lung infections above all. But I expect they will also find use in disinfecting operating theatres, rooms, surgical instruments and other medical equipment.

Are the mini-robots ready?
Yes. Five years ago I received a grant from the European Research Council. Thanks to it we selected and tested the materials for building the robots, created prototypes and verified their reliability.

When can we expect mini-robots to be used in medicine?
If they take the form of a drug, testing and approval will take decades. If they are applied as a food supplement with a natural substance, the approval regime is simpler. And as a disinfectant for hospitals they could be in use within a few months of finishing our two-year project, for which we received funding from the Neuron Endowment Fund.

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