Biophysical Society Thematic Meeting | Stockholm 2022

Physical and Quantitative Approaches to Overcome Antibiotic Resistance

Poster Abstracts

12-POS Board 12 ANTIMICROBIAL ACTION ON PERSISTER PHENOTYPES Ratnasri K 1 ; Rahul Roy 1,2 ; 1 Indian Institute of Science, Centre for BioSystems Science and Engineering, Bangalore, India 2 Indian Institute of Science, Chemical Engineering, Bangalore, India Bacterial persisters are a subset of phenotypic variants that exist in an isogenic bacterial population. They are characterised by their tolerance to harsh environments such as starvation and antibiotic exposure. Not only have persister bacteria been implicated in the recalcitrance of many infections, but recent evidence points towards persister cells serving as a precursor for onset of antibiotic resistance. Hence, understanding the formation and behaviour of persister bacteria is important for insights into emergence of antimicrobial resistance.Persistence is known to be a non-heritable and transient phenomenon occurring at very low frequencies, making the isolation and study of persisters harder. In addition, several different molecular pathways and physiological conditions have been shown to be connected to the persister phenotype, including cell dormancy or slow growth, reduced metabolic activity, activation of the stringent response and the involvement of toxin-antitoxin modules. In this study, we test the idea that a bacterial population when subjected to stress conditions, can enter persister-like state via multiple pathways. We enrich for persisters originating from different conditions from an exponentially growing bacterial culture. The enrichment is followed by a time-kill assay using the antibiotic Ofloxacin to measure the level of Ofloxacin tolerant persisters. While the enrichment based on reduced metabolic activity generates a 100 - fold increase in persisters, a prior antibiotic exposure yields only a 10-fold increase. We then examine the efficacy of various antibiotics and antimicrobial peptides (AMPs) in inhibiting the growth of the persister populations.

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