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Possible new antibiotics to circumvent antibiotic resistance

4 April 2022
Microbiologist Maurice Steenhuis has developed an innovative way of identifying new antibiotics to circumvent antibiotic resistance. Using this method, he has found three chemical substances that could be developed into a new class of antibiotics.

Antibiotic resistance, which entails bacteria becoming insensitive to antibiotics, is a massive and growing problem. The World Health Organisation predicts that ten million people will die from the consequences of antibiotic resistance annually by 2050. This figure is currently 700,000 people. “The problem could lead to mortality rates which are even higher than those due to the COVID-19 pandemic”, according to Steenhuis, PhD candidate at Vrije Universiteit Amsterdam and currently COVID-19 project leader at Sanquin in Amsterdam.

Stress assay effective
The results of Steenhuis’s PhD research show that what is known as a ‘stress assay’ is successful in identifying new antibacterial substances that act on the outer membranes of bacteria. To this end, he used the stress systems of bacteria. Steenhuis: “Just as people show a ‘fight-or-flight’ stress response to approaching danger, bacteria respond with stress to impulses from the environment, such as the presence of toxic substances (e.g. antibiotics) or food shortages.”

Steenhuis has developed a method in which bacteria fluoresce green as soon as they experience stress from coming into contact with antibacterial substances. More than 300,000 chemical substances have been tested with this new method and three substances were selected that probably act on the outermost membrane of bacteria and, as a result, weaken the bacteria.

Possible new antibiotics
Many factors contribute to the problem of antibiotic resistance, including the large-scale use of antibiotics in livestock farming and the excessive and sometimes incorrect use of antibiotics in healthcare. There have, furthermore, been hardly any new classes of antibiotics developed since 1980. Steenhuis: “If we are to combat antibiotic resistance, it is essential that we develop new antibiotics that kill bacteria in different ways to current antibiotics. This is why Joen Luirink (head of Molecular Microbiology at Vrije Universiteit Amsterdam) and I have jointly developed a method for identifying new antibiotics which focuses primarily on the outer membrane of gram-negative bacteria.”

Follow-up research is needed to show whether the substances found in this research can be developed further into a new class of antibiotics. The stress assay is currently being used by the European Lead Factory to test its library of more than 500,000 chemical substances for antibacterial activity.

Recently, VU microbiologist Joen Luirink, the associate professor who supervised Steenhuis in his research, received NWO funding of nearly one million euros for research on antibiotic resistance in collaboration with Leiden University.

Steenhuis' PhD will take place on April 19, 2022.