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

Hingley-Wilson, Suzie, Ma, Nan, Hu, Yin, Casey, Rosalyn, Bramming, Anders, Curry, Richard J., Tang, Hongying Lilian, Wu, Huihai, Butler, Rachel, Jacobs Jr., William R. , Rocco, Andrea and McFadden, Johnjoe (2020) Loss of phenotypic inheritance associated with ydcI mutation leads to increased frequency of small, slow persisters in Escherichia coli Proceedings of the National Academy of Sciences.

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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 highpersister 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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Hingley-Wilson, Suzies.hingley-wilson@surrey.ac.uk
Ma, Nan
Hu, Yin
Casey, Rosalyn
Bramming, Anders
Curry, Richard J.
Tang, Hongying Lilian
Wu, HuihaiH.Wu@surrey.ac.uk
Butler, RachelR.Shrimpton@surrey.ac.uk
Jacobs Jr., William R.
Rocco, AndreaA.Rocco@surrey.ac.uk
McFadden, JohnjoeJ.Mcfadden@surrey.ac.uk
Date : 6 February 2020
Funders : Biotechnology and Biological Sciences Research Council (BBSRC), Royal Society, National Institutes of Health
DOI : doi.10.1073/pnas.1914741117
Grant Title : BBSRC Grant
Copyright Disclaimer : Copyright © 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Uncontrolled Keywords : persistence | antibiotic resistance | phenotypic | microbiology | systems biology
Depositing User : James Marshall
Date Deposited : 19 Feb 2020 10:35
Last Modified : 19 Feb 2020 10:35
URI: http://epubs.surrey.ac.uk/id/eprint/853784

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