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Bacterial charity work leads to population-wide resistance

Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual endpoint isolates1–7. Less is known, however, about the population dynamics during the development of antibio...

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Autores principales: Lee, Henry H., Molla, Michael N., Cantor, Charles R., Collins, James J.
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936489/
https://www.ncbi.nlm.nih.gov/pubmed/20811456
http://dx.doi.org/10.1038/nature09354
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author Lee, Henry H.
Molla, Michael N.
Cantor, Charles R.
Collins, James J.
author_facet Lee, Henry H.
Molla, Michael N.
Cantor, Charles R.
Collins, James J.
author_sort Lee, Henry H.
collection PubMed
description Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual endpoint isolates1–7. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population’s less resistant constituents, in part, by producing indole, a signaling molecule generated by actively growing, unstressed cells8. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is enabled by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection9 whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other more vulnerable cells, enhancing the survival capacity of the overall population in stressful environments.
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spelling pubmed-29364892011-03-01 Bacterial charity work leads to population-wide resistance Lee, Henry H. Molla, Michael N. Cantor, Charles R. Collins, James J. Nature Article Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual endpoint isolates1–7. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population’s less resistant constituents, in part, by producing indole, a signaling molecule generated by actively growing, unstressed cells8. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is enabled by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection9 whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other more vulnerable cells, enhancing the survival capacity of the overall population in stressful environments. 2010-09-02 /pmc/articles/PMC2936489/ /pubmed/20811456 http://dx.doi.org/10.1038/nature09354 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Lee, Henry H.
Molla, Michael N.
Cantor, Charles R.
Collins, James J.
Bacterial charity work leads to population-wide resistance
title Bacterial charity work leads to population-wide resistance
title_full Bacterial charity work leads to population-wide resistance
title_fullStr Bacterial charity work leads to population-wide resistance
title_full_unstemmed Bacterial charity work leads to population-wide resistance
title_short Bacterial charity work leads to population-wide resistance
title_sort bacterial charity work leads to population-wide resistance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936489/
https://www.ncbi.nlm.nih.gov/pubmed/20811456
http://dx.doi.org/10.1038/nature09354
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