Loss of phenotypic inheritance associated with ydcI mutation leads to increased frequency of small, slow persisters in Escherichia coli

Suzanne M. Hingley-Wilson, Nan Ma, Yin Hu, Rosalyn Casey, Anders Bramming, Richard J. Curry, Hongying Lilian Tang, Huihai Wu, Rachel E. Butler, William R. Jacobs, Andrea Rocco, Johnjoe McFadden

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Whenever a genetically homogenous population of bacterial cells is exposed to antibiotics, a tiny fraction of cells survives the treatment, the phenomenon known as bacterial persistence [G.L. Hobby et al., Exp. Biol. Med. 50, 281–285 (1942); J. Bigger, The Lancet 244, 497–500 (1944)]. Despite its biomedical relevance, the origin of the phenomenon is still unknown, and as a rare, phenotypically resistant subpopulation, persisters are notoriously hard to study and define. Using computerized tracking we show that persisters are small at birth and slowly replicating. We also determine that the high-persister mutant strain of Escherichia coli, HipQ, is associated with the phenotype of reduced phenotypic inheritance (RPI). We identify the gene responsible for RPI, ydcI, which encodes a transcription factor, and propose a mechanism whereby loss of phenotypic inheritance causes increased frequency of persisters. These results provide insight into the generation and maintenance of phenotypic variation and provide potential targets for the development of therapeutic strategies that tackle persistence in bacterial infections.

Original languageEnglish (US)
Pages (from-to)4152-4157
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number8
DOIs
StatePublished - Feb 25 2020

Keywords

  • Antibiotic resistance
  • Microbiology
  • Persistence
  • Phenotypic
  • Systems biology

ASJC Scopus subject areas

  • General

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