Biophysical Society Thematic Meeting | Stockholm 2022

Physical and Quantitative Approaches to Overcome Antibiotic Resistance

Poster Abstracts

18-POS Board 18 ANTIBIOTIC RESISTANCE VIA BACTERIAL CELL SHAPE SHIFTING Nikola Ojkic 1 ; Diana Serbanescu 2 ; Shiladitya Banerjee 3 ; 1 Queen Mary University of London, School of Biological and Behavioural Sciences, London, United Kingdom 2 University College London, Department of Physics and Astronomy, London, United Kingdom 3 Carnegie Mellon University, Department of Physics, Pittsburgh, PA, USA Antibiotic resistance is one of the major threats to human society prompting urgent global response. Bacteria developed multiple strategies for antibiotic resistance by effectively reducing intracellular antibiotic concentrations or antibiotic binding affinities to their specific targets. Resistance commonly occurs via a reduction in porin expression, modulation of membrane lipid composition, horizontal gene transfer, increased expression level of efflux pumps and proteins that inactivate antibiotics, or via SOS response. Here we present a recently discovered pathway to antibiotic resistance that depends on the bacterial morphological transformation that promotes bacterial decrease of antibiotic influx to the cell. By analysing cell morphological data of different bacterial species under antibiotic stress, we find that bacterial cells robustly reduce surface-to-volume ratio in response to most types of antibiotics. Using quantitative modelling we show that by reducing the surface-to-volume ratio, bacteria can effectively reduce intracellular antibiotic concentration by decreasing antibiotic influx. The model predicts that bacteria can increase the surface-to-volume ratio to promote antibiotic dilution for membrane targeting antibiotics, in agreement with data on membrane-transport inhibitors. Using the particular example of ribosome-targeting antibiotics, we present a systems-level model for the regulation of cell shape under antibiotic stress and discuss feedback mechanisms that bacteria can harness to increase their fitness in the presence of antibiotics.

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