Antibiotic perseverance increases the risk of resistance development

Abstract

The rise of antibiotic-resistant bacterial infections poses a global threat. Antibiotic resistance development is generally studied in batch cultures which conceals the heterogeneity in cellular responses. Using single-cell imaging, we studied the growth response of Escherichia coli to sub-inhibitory and inhibitory concentrations of nine antibiotics. We found that the heterogeneity in growth increases more than what is expected from growth rate reduction for five out of the nine antibiotics tested. For two antibiotics (rifampicin and nitrofurantoin), we found that sub-populations were able to maintain growth at lethal antibiotic concentrations for up to 10 generations. This perseverance of growth increased the effective population size and led to an up to 40-fold increase in antibiotic resistance development in Gram-negative and Gram-positive species. We conclude that antibiotic perseverance is a common phenomenon across the bacterial kingdom that has the potential to impact antibiotic resistance development.