The development of the light microscope sparked the investigation of microorganisms that were not visible to the naked eye. Probably in the late 1600s, Antoni van Leeuwenhoek first detected bacteria, but there was no notion of their significance yet. In the 19th century, advanced by the works of Robert Koch and Louis Pasteur, the germ theory was proposed, stating that microorganisms are the cause of infectious diseases. In 1910, Paul Ehrlich developed the first synthetic anti-infective drug, a now obsolete arsenic-based substance named salvarsan. In 1928, Fleming discovered the first natural antibiotic, penicillin. Since then, microbiology has made tremendous progress and most of the antibiotic drugs used today were discovered in the Golden Age of antibiotic discovery between the 1940s and 1960s.
Antibiotics can affect different structures and processes in bacteria. Polypeptide antibiotics, for example, change the permeability of the bacterial membrane (e.g. Gramicidin A). Other substances, like b-lactam antibiotics (e.g. Penicillin) or glycopeptides (e.g. Vancomycin) can disrupt the synthesis of the cell wall. Furthermore, protein synthesis can be blocked, e.g. by aminoglycosides (e.g. Kanamycin A) or tetracyclines (e.g. Tetracycline). Synthetic antibiotics like nitrofurans (e.g. Nitrofurantoin) or azoles (e.g. Metronidazole) disrupt the DNA synthesis. Another important class of antibiotics are sulfonamides, which inhibit important metabolic pathways like folate synthesis.
Despite the variety of antibiotic substance classes, we are now facing new challenges concerning bacterial infections. The broad use and misuse of antibiotics led to the rapid development of resistance, causing emerging and re-emerging bacterial infections and multiresistant bacteria. At the same time, the development of new antibiotics has slowed down considerably. In order to overcome the threat of a post-antibiotic era, the early drug discovery steps need to be promoted and new substance classes need to be explored to keep pace with the fast-developing resistance mechanisms.
The switchSENSE® technology can be applied to gain a deeper understanding of the mechanism of action of antibiotics as well as of the biology of bacteria and can thus help to create innovative antibiotic solutions.
→ Examine and screen compounds affecting nucleic acid synthesis in bacteria
→ Investigate protein-protein interactions as new targets
→ Elucidate the biology of bacteria by discovering molecular interactions
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2020 I Bioscience Reports (open access)
→ Tailored peptide phenyl esters block ClpXP proteolysis by an unusual breakdown into a heptamer‐hexamer assembly
2019 I Angewandte Chemie
→ Molecular mechanism governing ratio-dependent transcription regulation in the ccdAB operon
2017 I Nucleic Acids Research (open access)
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