Cell membranes are a fundamental component of all living cells, whether they are bacterial, animal, plant, or fungal. However, not all cell membranes are equal: depending on the organism, they differ in composition and structure. This diversity presents promising avenues for the development of novel antibiotics, compounds that specifically target bacterial cells and thus combat bacterial infections. The pressing need for new antibiotics arises from the fact that many bacteria have either developed or are developing resistance to those antibiotics that are now used in the clinic.
To effectively design antibiotics that target cell membranes, a thorough understanding of how bacterial membranes are constructed and function is essential. Breukink and his team are dedicated to unraveling these details in order to be able to find new antibiotics.
I believe that fungi produce other intriguing compounds waiting to be discovered, that can help us in our cause.
Prof. Eefjan Breukink
A leaky outer membrane
Breukink illustrates his approach with an example. Breukink: "Many of the bacteria posing significant challenges at the moment possess two membranes. Conventional antibiotics, which effectively target single-membrane bacteria, are blocked by the second, outer membrane. Therefore, my aim is to use inventive methods to find compounds that induce a leakage of the outer membrane."But where does one find such compounds? Breukink turns to nature for inspiration and resources. He collaborates with the Westerdijk Institute, known for its vast collection of fungi. Breukink: "Fungi gifted us with penicillin, the first-ever antibiotic. However, I believe that fungi produce other intriguing compounds waiting to be discovered, that can help us in our cause."
Lipid II
Among his pursuits, the chemist explores compounds that target a molecule known as Lipid II. This molecule resides within the bacterial membrane and plays a crucial role in the synthesis of bacterial cell walls, which serve to fortify and shield the cell.According to the researcher, Lipid II presents an intriguing target for potential antibiotics, due to the unlikely development of bacterial resistance against substances that target this molecule. Bacterial resistance typically arises when the target of an antibiotic undergoes modifications. For instance, if an antibiotic targets a specific protein, genetic mutations can alter the protein in a way that allows it to retain its functionality while rendering the antibiotic ineffective.
Breukink: "Given that Lipid II is produced and utilized by various proteins, specific segments of the molecule are essentially resistant to change. Consequently, bacteria are less prone to developing resistance against antibiotics that specifically target Lipid II."
As a chemist, I enjoy hands-on involvement, but I also value collaborative efforts to address these questions.
Prof. Eefjan Breukink
Collaborations
Breukink completed his chemistry studies as well as his PhD at Utrecht University. His research on cell membranes is highly interdisciplinary, incorporating elements of chemistry, microbiology, genetics, and more. As a result, Breukink engages in extensive collaborations with diverse research institutes in Utrecht, such as joint efforts to determine the structure of potentially interesting compounds. Breukink: "I work in a question-driven manner, focusing on research questions that I find intriguing. Utrecht is home to numerous outstanding research groups. As a chemist, I enjoy hands-on involvement, but I also value collaborative efforts to address these questions."Breukink’s team-oriented mindset extends beyond his professional endeavors. During his leisure time, the researcher passionately participates in field hockey and even secured a gold medal at the 2022 World Hockey Masters Championships. Breukink: "Having been involved in team sports throughout my entire life undoubtedly influences how I function and work with others.