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BP: Fachverband Biologische Physik

BP 6: Bacterial Biophysics I

BP 6.2: Talk

Monday, March 18, 2024, 15:30–15:45, H 1028

Understanding the mechanisms of novel and existing antibiotics at the single-cell level — •Lars Renner¹, Felix Wong², James Collins², Jens Friedrichs¹, and Ralf Helbig¹ — ¹Leibniz-Institute of Polymer Research, Max Bergmann Center of Biomaterials, Dresden, Germany — ²Massachusetts Institute of Technology, Cambridge, MA, USA

Many existing antibiotics are becoming increasingly ineffective causing antibiotic resistance in bacteria. Antibiotics have different molecular targets, however, even after decades of medical use, many effects of antibiotics on bacteria are still unknown. We investigate the mechanistic mode of action of antibiotics, particularly at the single cell level. Using various techniques, we are corroborating the cellular physiology and biochemical regulation as well as the different molecular mechanism downstream caused by the application of antibiotics, specifically for aminoglycoside, beta-lactams and quinolones. We have observed that cell death is preceded by cytoplasmic condensation for aminoglycosides and quinolones. When beta-lactams are used, cell wall synthesis is significantly disrupted, resulting in cellular lysis, which we are studying both in bulk and at the single cell level. By elucidating the molecular effects, we hope to address the problem of antibiotic misuse and the associated potential antibiotic resistance. In addition, we are using machine-learning approaches to determine structure-function relationships which in turn are used to identify and discover novel, underutilized or untouched structural classes of antibiotics with explainable deep learning to fight the antibiotic resistance crisis.

Keywords: antibiotics; cell mechanics; cell wall; turgor pressure