A test now available could help rapidly determine whether a bacterial infection is resistant to antibiotics of last resort.
The test kit developed using Imperial technology by Bruker Daltonics, a global mass spectrometry and diagnostic company, can be used to test hospital patients on-site for bacterial infections that are resistant to colistin and other members of the antibiotic family known as polymyxins.
Polymyxins are used as a last resort antibiotic because they are often effective even against superbugs that are otherwise antibiotic-resistant. The spread of bacterial resistance even to these last-line antibiotics is therefore a serious threat to human health.
The new test can be carried out at the point of need using equipment that many hospitals are already equipped with, avoiding the present need to send samples to off-site laboratories. It has been developed as a mass spectrometry-based application for the latest generation of MALDI Biotyper instruments, which can operate in negative ion mode.
Preventing the spread of antibiotic resistance
By reducing the time from sample to result from two days to 30 minutes, the test could help hospitals quickly control the spread of polymyxin resistance by implementing appropriate patient isolation or hygiene measures. The kit is currently available for research use and future versions designed for diagnostic use have the potential to improve the quality of patient care by allowing doctors to identify the most effective treatments more quickly and avoid giving antibiotics to patients with resistant infections.
Importantly, the test kit also helps indicate how transmissible a case of antibiotic resistance is. The DNA that causes a bacterium to be antibiotic-resistant is sometimes found in its chromosome, where it is copied from parent to offspring. However, it can sometimes be found in the bacterium’s plasmid, a separate DNA molecule, where it can be copied from one bacterium to another. Resistance caused by plasmid DNA can spread very rapidly if it is not detected, and the new technology could play a vital role in helping prevent this.
The complete solution provided by Bruker Daltonics comes also with a dedicated software module that discriminates between chromosome- and plasmid-encoded resistance types and allows technicians to understand the results easily without extensive additional training.
From bench to bedside
Dr Gerald Larrouy-Maumus (Department of Life Sciences and the MRC Centre for Molecular Bacteriology and Infection), the lead inventor of the technology, said: “By working with Bruker, which is a world leader in mass spectrometry for diagnostics, we have been able to go from the lab bench to the public, to address an important clinical need.”
The MBT Lipid Xtract™ Kit, launched in September 2021, is available worldwide (except USA) for research use, and its creators hope it will in due course be validated and approved as a clinical diagnostic.
The kit was developed using research by Dr Larrouy-Maumus and colleagues, who made use of academic insights into the mechanisms of bacterial resistance to polymyxins, which involve a change in the electrical charge of a bacterium’s lipid molecules that prevents antibiotics from attracting them.
The team used a pump priming award from the Faculty of Natural Sciences and Confidence in Concept to translate this basic research into a testing technology that differentiates from the most widespread approach which is currently using spectral profiles of proteins rather than analysing the profile of lipids. This was then further developed by Bruker. The team is working as part of a research partnership with the company on further research and development, including innovations that could help address the global challenge of antibiotic resistance.
The technology is an example of important work carried out by Imperial's multidisciplinary MRC Centre for Molecular Bacteriology and Infection. Professor José Penadés, the Centre's Director, said: "This fantastic work by Gerald and colleagues is a great example of the innovative and state-of-the-art approaches under development at our Centre, which uniquely focuses on bacterial pathogens."
A global challenge
Dr Larrouy-Maumus said: “Antibiotic resistance, along with climate change and the COVID-19 pandemic, is a huge problem. If we do nothing by 2050, 10 million deaths a year will be attributed to antibiotic resistance, and we will see a huge economic loss of around 100 trillion dollars. So of course, we need to think about how we can address this global challenge. The test we have created is an important tool.”
Professor Anne Dell, head of Imperial’s Department of Life Sciences, added: “I’m very proud of the work that Gerald and colleagues have done with our partners at Bruker Daltonics to translate hard-won academic insights first into an invention, and now a commercially available technology, that promises to play an important role in addressing antibiotic resistance and ultimately in saving lives.”
