Year: 2021
Type: article
Abstract: Persistent bacterial infections do not respond to current antibiotic treatments and thus present a great medical challenge. These conditions have been linked to the formation of dormant subpopulations of bacteria, known as persister cells, that are growth-arrested and highly tolerant to conventional antibiotics. Here, we report a new strategy of persister control and demonstrate that minocycline, an amphiphilic antibiotic that does not require active transport to penetrate bacterial membranes, is effective in killing Escherichia coli persister cells [by 70.8 ± 5.9% (0.53 log) at 100 μg/mL], while being ineffective in killing normal cells. Further mechanistic studies revealed that persister cells have reduced drug efflux and accumulate more minocycline than normal cells, leading to effective killing of this dormant subpopulation upon wake-up. Consistently, eravacycline, which also targets the ribosome but has a stronger binding affinity than minocycline, kills persister cells by 3 logs when treated at 100 μg/mL. In summary, the findings of this study reveal that while dormancy is a well-known cause of antibiotic tolerance, it also provides an Achilles' heel for controlling persister cells by leveraging dormancy associated reduction of drug efflux.
Source: PLoS Pathogens
Institutions: Syracuse University, Binghamton University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,575
Funders: National Science Foundation, Syracuse University, State University of New York, National Institutes of Health, State University of New York Upstate Medical University, National Institute of Biomedical Imaging and Bioengineering, Division of Materials Research, Division of Graduate Education, Division of Chemical, Bioengineering, Environmental, and Transport Systems
Awards: Integrating synthetic biology approaches with patterned biofilm formation to investigate bacterial persistence in heterogeneous structures, Developing Rational Design Principles for Textured Medical Device Surfaces, G40853927, Controlling Catheter-Associated Urinary Tract Infections Using Smart Catheters with Rationally Designed Active Topographies, G7171895946
OpenAlex ID: W4200082261