Bacteria become resistant to antibiotics through changes in their DNA - changes which can now be found, through the use of modern DNA sequencing technology. A new international research network, led by Chalmers and Erasmus University Medical Center in the Netherlands, will help bring recent advances in DNA sequencing to bacterial diagnostics in healthcare settings.
Clinical microbiology laboratories rely today mainly on cultivation to identify bacteria resistant to antibiotics. Bacteria collected from the patient are grown alongside various types of antibiotics to find drugs that work against them - a method that can take days, or in some cases, weeks.
"Cultivation will remain important, but with the increasing number of infections caused by resistant bacteria, it may not be enough," explains Erik Kristiansson, Professor of Mathematical Sciences at Chalmers. "We need to improve diagnostics to provide faster and more accurate results."
DNA sequencing - a technology that can be used to characterise all the genes a bacterium carries in its genome - can provide just that. But even though the technology is rapidly improving, several challenges need to be solved before it can be effectively applied in routine diagnostics.
Big data expertise a key requirement
Erik Kristiansson is one of two leaders for the new research network, Integrating Microbial Sequencing and Platforms for Antimicrobial Resistance, which aims to provide solutions for these challenges. In this work, an action plan will be developed to increase the adoption rate of sequencing-based diagnostics.
As an expert in bioinformatics and artificial intelligence, he works with key questions in how the vast and complex data generated by DNA sequencing of bacteria should be handled and properly interpreted. Here, a major task is to develop and implement data analysis methods that can correctly identify the changes that make bacteria resistant to antibiotics.
Other challenges are to ensure that the execution of the DNA sequencing is done properly and accurately and that the genetic databases - which the methods rely upon - are of sufficient quality.
"One strength of our network is that it is interdisciplinary," says Erik Kristiansson. "There are experts from both academia and industry as well as from scientific areas including infectious diseases, bacteriology, computer science and statistics. This will allow us to take a holistic approach to the many factors that affect the spread of resistant bacteria."
"We aim to facilitate the implementation of DNA sequencing as a technique in routine diagnostics in hospitals globally. Here, training personnel to utilise this new technique is an important task. Knowledge dissemination and education will therefore be a part of the network."
Methods for both fighting resistance and managing outbreaks
DNA sequencing has the potential to reduce antibiotic use and thereby make it harder for bacteria to become resistant. By analysing the entire genome of an infecting bacterium, physicians can be provided with all the information needed for starting a patient-tailored antibiotic treatment at an early stage.
In the best-case scenario the bacterium is not resistant and the patient can receive a narrow-spectrum antibiotic, that is, an antibiotic that is more specific and only kills a limited number of bacterial species at the same time. This reduces the risk that other bacteria, for example those that live naturally in and on the human body, become resistant. In the worst case, the infection is instead caused by a bacterium that has developed resistance against a wide range of antibiotics.
"It can then become a matter of finding a type of antibiotic that will work at all. In the event of a serious infection, rapid and accurate diagnosis can be life-saving," says Erik Kristiansson. DNA sequencing can also be instrumental in preventing outbreaks of bacterial infections in hospitals. By monitoring the bacteria that spread within health care settings, resistant and virulent pathogens can be identified at an early stage. Various management strategies, such as isolation of patients, can then be used to disrupt the chain of transmission.
Virus sequencing is carried out with the same technology and expertise
The work done by the network will enable healthcare and clinical laboratories to adopt DNA sequencing for all kinds of microorganisms. This also applies to viruses - a very relevant area during the current pandemic - where sequencing can be used as a tool to monitor coronavirus mutations. In the long run, veterinary medicine may also be able to benefit from the results of the network.
Practices for the use of antibiotics vary greatly between countries, and there is a link between widespread use and serious problems with antibiotic resistance. But even though antibiotic resistance can be partially combated within a country through measures such as restrictive antibiotic use, the problem is in essence global. Indeed, antibiotic-resistant bacteria spread rapidly around the world as a result of international travel. The network therefore has a global perspective and includes 14 experts from 8 different countries.
"When we present our results in two years, we aim especially to contribute with solutions to countries that still have a long way to go when it comes to sustainable antibiotic use," says Erik Kristiansson. "Determining the most efficient way to reach this point is an important part of the holistic approach the network will use."
Text: Johanna Wilde and Joshua Worth
Photo: Nachiket P Marathe
More about the network: Integrating Microbial Sequencing and Platforms for Antimicrobial Resistance
- Coordinated by Erik Kristiansson at the Department of Mathematical Sciences at Chalmers ([email protected]) and John P. Hays at Erasmus University Medical Center Rotterdam ([email protected]).
- Financed nationally by Sweden and the Netherlands, through the organisation Joint Programming Initiative on Antimicrobial Resistance. The organisation is a global cooperation platform of 28 countries for combatting antibiotic resistance. The secretariat is located at the Swedish Research Council.
- The network and the organisation operate from a One Health-perspective, where the many disparate factors that affect the development and spread of resistant bacteria are considered jointly.
