Bacteria share resistance information

There are numerous mechanisms that cause bacteria to become resistant to antibiotics – and new ones are constantly emerging. All these mechanisms are encoded in the genetic information of the bacteria. Some of these genetic codes can also be found on mobile DNA elements called plasmids, which can be transferred between bacteria. This facilitates the transmission of antibiotic resistance, including between different species. Plasmids therefore also play an important role in the development and spread of antibiotic resistance. But exactly what enables or inhibits their exchange between bacteria is still not known. A research team headed by Sebastian Bonhoeffer at ETH Zurich has now gained in-depth insights into these issues – and thereby discovered previously unknown ways in which antibiotic resistance is spread.

Successful predictions on the transfer of resistance genes

Under artificial conditions, the researchers initially brought together various bacterial populations and, using specially developed methods, observed how quickly certain resistance plasmids spread between these populations. They found numerous factors that determine the rate at which the plasmids are transferred. Both the host – the bacterium that transmits a plasmid – and the recipient as well as the plasmid play a key role in this process. Thanks to their knowledge of various possible influencing factors, Bonhoeffer and his team were able to develop a model that can be used to predict the rate at which plasmids spread for certain bacteria and plasmids. In tests with clinically relevant bacteria and plasmids obtained from samples from University Hospital Basel, these predictions were confirmed both under artificial conditions and in animal experiments with mice.

Previously unknown routes of spread

In animal experiments, the researchers also observed how certain pathogens of the Salmonella species in intestinal tissue manage to survive a treatment with antibiotics by adjusting their metabolism and falling into a kind of deep sleep. Although these “sleepers” are not antibiotic-resistant themselves, some of them carry resistance plasmids. The researchers have now shown, for the first time, that such bacteria pass on their resistance plasmids to other bacterial species when they reactivate their metabolism.

Basis for interventions

These results give an insight – at a hitherto unprecedented level of detail – into the role of plasmids in the spread of antibiotic resistance. They show that intervention measures should focus not just on pathogens whose resistance is enabled by plasmids. Rather, they should also consider related bacteria, including pathogens, since these serve as plasmid reservoirs and are therefore able to increase the spread of resistance plasmids.

The mathematical models and bioinformatic methods developed during the project can identify specific situations that facilitate the sharing of resistance information between pathogens. This allows doctors to take corresponding countermeasures in good time during the course of an illness. It also provides a toolkit to help us obtain a more detailed understanding of the interactions between humans, animals and the environment in the spread of antibiotic resistance.

February 2022

Towards quantification of the contribution of plasmids to the spread of antibiotic resistance