Michaela Wenzel’s group studies the molecular mechanisms of antibiotic action and resistance in living bacteria with the aim to improve the fundamental knowledge of how antibiotics interact with bacterial cells. This knowledge is pivotal to develop new and more sustainable antibiotics and novel antibacterial strategies.
The discovery of antibiotics such as penicillin revolutionized modern medicine. Formerly deadly diseases became easily treatable and infections following childbirth or surgical procedures could be effectively medicated. However, this privileged situation could change drastically over the next years. Bacteria possess a remarkable capability to genetically adapt and become increasingly resistant to existing antibiotics. Only few new antibiotics have been developed in the last decades, which makes it increasingly difficult to keep up with the development of bacterial resistance. To reverse this trend and prevent a fallback into a pre-antibiotic era, we need to advance antibiotic discovery and minimize the development and spread of antibiotic resistance.
The key to antibiotic sustainability is to develop substances that leave little possibility for bacteria to adapt and become resistant too fast. One strategy to achieve this is to target the bacterial cell envelope. This complex structure, which consists of one or two lipid membranes and a cell wall composed of sugars and amino acids, separates the cell from the outside environment. An intact cell envelope is essential for bacteria to survive and its complexity largely precludes spontaneous resistance mutations. Moreover, changes in cell envelope structure are poorly tolerated, which leaves less possibilities for bacteria to become resistant. Antibiotics that impair cell envelope functions, such as penicillin, are very successful in treating infections. However, to date only a tiny fraction of possible cell envelope targets is clinically exploited, leaving plenty of currently unused potential.
To more successfully exploit this promising antibiotic target structure, it is necessary to first understand how antibiotics interfere with it and what measures bacteria have to adapt their cell envelopes to antibiotic exposure. Surprisingly little detail is known about these mechanisms, especially considering that the first antibiotics were discovered over a century ago. Recent advances in microscopy technologies have opened up a whole new dimension to study formerly inaccessible details.
In Michaela Wenzel’s lab a combination of high-end single cell microscopy and proteome-based techniques are used to elucidate the mechanisms underlying antibiotic action and resistance to better understand how the cell envelope can be targeted by future antibiotics. The longtime goal of this research is to identify promising new antibiotic targets within the bacterial cell envelope and to develop strategies to target bacterial adaptation and resistance systems with the aim to re-sensitize resistant bacteria to existing antibiotics and prevent too fast resistance development of the next generation of antibiotics.