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Article

Bistable Bacterial Growth Dynamics in the Presence of Antimicrobial Agents

by 1,†, 1,†, 2, 1,* and 2,*
1
Department of Biomolecular Sciences, 206 Nella and Leon Benoziyo Building for Biological Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel
2
Department of Computer Science and Applied Mathematics, 211 Jacob Ziskind Building, The Weizmann Institute of Science, Rehovot 76100, Israel
*
Authors to whom correspondence should be addressed.
Nelly Frenkel and Ron Saar Dover contributed equally to this work.
Received: 21 December 2020 / Revised: 11 January 2021 / Accepted: 13 January 2021 / Published: 18 January 2021
(This article belongs to the Section Antimicrobial Peptides)
The outcome of an antibiotic treatment on the growth capacity of bacteria is largely dependent on the initial population size (Inoculum Effect). We characterized and built a model of this effect in E. coli cultures using a large variety of antimicrobials, including conventional antibiotics, and for the first time, cationic antimicrobial peptides (CAMPs). Our results show that all classes of antimicrobial drugs induce an inoculum effect, which, as we explain, implies that the dynamic is bistable: For a range of anti-microbial densities, a very small inoculum decays whereas a larger inoculum grows, and the threshold inoculum depends on the drug concentration. We characterized three distinct classes of drug-induced bistable growth dynamics and demonstrate that in rich medium, CAMPs correspond to the simplest class, bacteriostatic antibiotics to the second class, and all other traditional antibiotics to the third, more complex class. These findings provide a unifying universal framework for describing the dynamics of the inoculum effect induced by antimicrobials with inherently different killing mechanisms. View Full-Text
Keywords: microbiology; antibiotics; antimicrobial peptides; inoculum effect; mathematical modeling of infection microbiology; antibiotics; antimicrobial peptides; inoculum effect; mathematical modeling of infection
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MDPI and ACS Style

Frenkel, N.; Saar Dover, R.; Titon, E.; Shai, Y.; Rom-Kedar, V. Bistable Bacterial Growth Dynamics in the Presence of Antimicrobial Agents. Antibiotics 2021, 10, 87. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010087

AMA Style

Frenkel N, Saar Dover R, Titon E, Shai Y, Rom-Kedar V. Bistable Bacterial Growth Dynamics in the Presence of Antimicrobial Agents. Antibiotics. 2021; 10(1):87. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010087

Chicago/Turabian Style

Frenkel, Nelly, Ron Saar Dover, Eve Titon, Yechiel Shai, and Vered Rom-Kedar. 2021. "Bistable Bacterial Growth Dynamics in the Presence of Antimicrobial Agents" Antibiotics 10, no. 1: 87. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010087

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