Persister control by leveraging dormancy associated reduction of antibiotic efflux

Sweta Roy, Ali Adem Bahar, Huan Gu, Shikha Nangia, Karin Sauer, Dacheng Ren

Research output: Contribution to journalArticlepeer-review

Abstract

Persistent bacterial infections do not respond to current antibiotic treatment 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.

Original languageEnglish (US)
Article numbere1010144
JournalPLoS Pathogens
Volume17
Issue number12
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Fingerprint

Dive into the research topics of 'Persister control by leveraging dormancy associated reduction of antibiotic efflux'. Together they form a unique fingerprint.

Cite this