Researchers break resistant bacteria’s defence against antibiotics

Researchers from the University of Copenhagen have discovered a method with which antibiotics can have an effect on pathogenic bacteria that are naturally resistant to treatment. In brief, the method targets the bacterium’s energy centre, making it easier for antibiotics to penetrate the bacteria cell and kill it.

Bacteria like staphylococci can cause serious diseases, and today the main form of treatment is antibiotics. However, seeing as staphylococci are naturally resistant to some forms of antibiotics, the options for fighting staphylococci infections are limited. Now Danish researchers have made an important discovery, which may make it possible to affect naturally resistant bacteria, ensuring that they can be treated with antibiotics. Using a simple method, the researchers are able to eliminate the barrier that previously prevented antibiotics from penetrating the bacteria cell and having an effect. Their results have just been published in the scientific journal mBio.

‘We have taken a somewhat alternative approach in our attempt to find a solution for fighting antibiotic resistance. Instead of looking for new antibiotics, we have chosen to look at what it takes to make known antibiotics effective against naturally resistant bacteria. In this way we have discovered a way to affect the bacteria and thus make it responsive to treatment’, says Postdoc Martin Vestergaard from the Department of Veterinary and Animal Sciences.

Difference in Bacteria Structure Is Vital to the Effect of Antibiotics

A main focus of the researchers has been examining how bacteria react when exposed to stress in the form of antibiotics. The researchers have studied the mechanisms and defence systems that make staphylococci naturally resistant.

Resistant bacteria have a different structure, and they do not have the same cell membrane as non-resistant bacteria, which may affect whether antibiotics are able to penetrate the cell. Therefore, the researchers have focussed on how they can change the structure of resistant bacteria, making them more responsive to antibiotics treatment.

Excipient Breaks the Defence Mechanism of Bacteria

In connection with very basic studies of staphylococci the researchers were surprised to learn that by inhibiting the energy centre of the bacteria they could make the bacteria more responsive to polymyxins. Polymyxins are an antibiotic generally used to treat salmonella and E. coli infections, but which are unable to penetrate staphylococci. The researchers have therefore tried to remove the barrier by adding an active excipient. The excipient penetrates, binds to and thus inhibits the energy centre of the bacterium. This alone does not kill the bacterium, but it makes it easier for antibiotics to penetrate the barrier and enter the bacterium where they may have an effect.

‘Developing new antibiotics is expensive and time-consuming, and if we are to find new ways of fighting antibiotic resistance, we need to think along new lines. We have therefore focussed on existing and approved antibiotics, which together with an excipient can suddenly have an effect on naturally resistant bacteria. Now it is interesting to see whether we can use the same method on other types of resistant bacteria than staphylococci’, says Professor Hanne Ingmer from the Department for Veterinary and Animal Sciences. She suggests that the new discovery may prove an important tool in the hospitals’ toolbox in their fight against resistant bacteria, and it shows that new applications of known antibiotics can help solve the problem of antibiotic resistance.

The article has just been published and can be read in the scientific journal mBio.

Source: University of Copenhagen