Patricia J Hare1,2, Hanna E Englander1,3, Wendy W K Mok1. 1. Department of Molecular Biology & Biophysics, UCONN Health, Farmington, Connecticut, USA. 2. School of Dental Medicine, UCONN Health, Farmington, Connecticut, USA. 3. Department of Physiology & Neurobiology, University of Connecticut, Storrs, Connecticut, USA.
Abstract
AIMS: Bacterial persisters are rare phenotypic variants in clonal bacterial cultures that can endure antimicrobial therapy and potentially contribute to infection relapse. Here, we investigate the potential of leveraging microbial interactions to disrupt persisters as they resuscitate during the post-antibiotic treatment recovery period. METHODS AND RESULTS: We treated stationary-phase E. coli MG1655 with a DNA-damaging fluoroquinolone and co-cultured the cells with probiotic E. coli Nissle following antibiotic removal. We found that E. coli Nissle reduced the survival of fluoroquinolone persisters and their progeny by over three orders of magnitude within 24 h. Using a bespoke H-diffusion cell apparatus that we developed, we showed that E. coli Nissle antagonized the fluoroquinolone-treated cells in a contact-dependent manner. We further demonstrated that the fluoroquinolone-treated cells can still activate the SOS response as they recover from antibiotic treatment in the presence of E. coli Nissle and that the persisters depend on TolC-associated efflux systems to defend themselves against the action of E. coli Nissle. CONCLUSION: Our results demonstrate that probiotic bacteria, such as E. coli Nissle, have the potential to inhibit persisters as they resuscitate following antibiotic treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacterial persisters are thought to underlie chronic infections and they can lead to an increase in antibiotic-resistant mutants in their progenies. Our data suggest that we can leverage the knowledge we gain on the interactions between microbial strains/species that interfere with persister resuscitation, such as those involving probiotic E. coli Nissle and E. coli MG1655 (a K-12 strain), to bolster the activity of our existing antibiotics.
AIMS: Bacterial persisters are rare phenotypic variants in clonal bacterial cultures that can endure antimicrobial therapy and potentially contribute to infection relapse. Here, we investigate the potential of leveraging microbial interactions to disrupt persisters as they resuscitate during the post-antibiotic treatment recovery period. METHODS AND RESULTS: We treated stationary-phase E. coli MG1655 with a DNA-damaging fluoroquinolone and co-cultured the cells with probiotic E. coli Nissle following antibiotic removal. We found that E. coli Nissle reduced the survival of fluoroquinolone persisters and their progeny by over three orders of magnitude within 24 h. Using a bespoke H-diffusion cell apparatus that we developed, we showed that E. coli Nissle antagonized the fluoroquinolone-treated cells in a contact-dependent manner. We further demonstrated that the fluoroquinolone-treated cells can still activate the SOS response as they recover from antibiotic treatment in the presence of E. coli Nissle and that the persisters depend on TolC-associated efflux systems to defend themselves against the action of E. coli Nissle. CONCLUSION: Our results demonstrate that probiotic bacteria, such as E. coli Nissle, have the potential to inhibit persisters as they resuscitate following antibiotic treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacterial persisters are thought to underlie chronic infections and they can lead to an increase in antibiotic-resistant mutants in their progenies. Our data suggest that we can leverage the knowledge we gain on the interactions between microbial strains/species that interfere with persister resuscitation, such as those involving probiotic E. coli Nissle and E. coli MG1655 (a K-12 strain), to bolster the activity of our existing antibiotics.
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