Researchers forecast how antibiotic resistance spreads among bacteria

Disease and treatment 25. jul 2021 3 min Professor Morten Otto Alexander Sommer Written by Kristian Sjøgren

Researchers can now identify which bacteria can exchange antibiotic resistance genes with each other. This enables researchers to predict more easily when pathogenic bacteria might develop resistance to various types of antibiotics. The discovery may also identify existing antibiotics that should be used more often.

Bacteria can exchange genes with one another.

This means that antibiotic resistance genes can be transferred from one bacterium to another, which then also becomes antibiotic resistant.

Antibiotic resistance is a huge public health problem, and the exchange of antibiotic resistance genes between pathogenic bacteria is a black box that can harbour all sorts of horrific scenarios.

In a new study, researchers in Denmark used genome data from several thousand types of bacteria to map which bacteria have the potential to transfer antibiotic resistance genes to one another and thereby probably become resistant to various antibiotics.

“This approach enables us to predict which resistance genes might transfer to the pathogenic bacteria, which is valuable information for those who develop antibiotics or work in public health,” explains a researcher behind the study, Morten Sommer, Professor, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby.

The research has been published in Nature Communications.

Bacteria can transfer antibiotic resistance in two ways

Morten Sommer and colleagues have strived for 10 years to understand how bacteria disseminate antibiotic resistance.

Bacteria can develop resistance to antibiotics in two ways.

· Parts of their own genome can mutate and thus make them resistant to an antibiotic.

· The other way is inheriting resistance from another bacterium in horizontal gene transfer, with antibiotic resistance genes being transferred from one bacterium to another on a plasmid, a small circular fragment of genetic material.

Morten Sommer investigated this horizontal transfer of antibiotic resistance genes between bacteria.

“Antibiotic resistance can develop in many types of bacteria: those in a water treatment plant, in the soil or in people’s intestines, including pathogenic bacteria. This also means that the pathogenic bacteria can acquire an antibiotic resistance gene from intestinal bacteria and thus become resistant to a relevant antibiotic. The reservoir for antibiotic resistance is therefore much larger than just the pathogenic bacteria. But so far, we have lacked understanding of which bacteria have the potential to exchange antibiotic resistance genes with one another,” says Morten Sommer.

Mapping the antibiotic resistance gene exchange network among bacteria

Morten Sommer and colleagues analysed all the available genetic information from thousands of types of bacteria that have had their genome mapped. They paid particular attention to the genetic code for antibiotic resistance genes in plasmids.

Using advanced mathematical models, the researchers mapped how antibiotic resistance genes probably were transferred between the bacteria. This enabled them to classify the bacteria into groups based on how well they transfer antibiotic resistance genes to one another.

Many pathogenic bacteria are especially good at sharing antibiotic resistance genes, but non-pathogenic bacteria can also do this.

“We have classified the bacteria into groups of between two and more than 20 bacteria that are especially good at transferring antibiotic resistance genes to one another. These are called gene exchange networks. We also found that the antibiotic resistance genes are not transferred individually but together with auxiliary factors, which are small genetic sequences located next to the antibiotic resistance genes. We have mapped them in all the genetic material and have thereby obtained even better insight into the transfer mechanisms,” explains Morten Sommer.

Morten Sommer explains that a gene exchange network can simply be summarised as a tendency that, for example, resistance gene A is often transferred to plasmid B, with a specific transfer mechanism between bacteria C and D.

Helping to regulate the use of new types of antibiotics

Morten Sommer elaborates that the discovery can be used to guide efforts to forecast and limit the emergence of antibiotic resistance in the future.

If researchers discover a new antibiotic resistance gene in a soil bacterium, they can study its gene exchange network and thereby assess the risk that the antibiotic resistance gene will transfer to a pathogenic bacterium, potentially resulting in public health problems.

The researchers partly validated the predictions using an independent genome data set and subsequently found that the bacteria they identified as potential recipients of antibiotic resistance genes actually developed antibiotic resistance.

Mapping the gene exchange networks can also be useful in developing new forms of antibiotics, because this can help to determine how quickly pathogenic bacteria will develop resistance to new types of antibiotics.

Morten Sommer explains that all new antibiotics are held in reserve so that they can be used against extremely antibiotic-resistant bacteria when all other types fail. Knowing for how long an antibiotic might be effective before the bacteria probably become resistant would therefore be useful. The new mapping may help to determine this.

In addition, the mapping might also help to make some of the types of antibiotics that are currently being held in reserve more available.

“LEO Pharma has developed an antibiotic for urinary tract infections, pivmecillinam, and despite several decades of use, bacteria have developed almost no resistance to it. If a new or existing antibiotic only has a slight potential for developing antibiotic resistance, it could be used more often than otherwise,” says Morten Sommer.

Forecasting the dissemination of antibiotic resistance genes across bacterial genomes” er udgivet i Nature Communications. In 2018, the Novo Nordisk Foundation awarded a Challenge Programme grant to Morten Sommer, Professor, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, for the project Design and Engineering of Biological Molecules and Systems.

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