The Genome-Wide Interaction Network of Nutrient Stress Genes in <named-content content-type="genus-species">Escherichia coli</named-content>

ABSTRACT Conventional efforts to describe essential genes in bacteria have typically emphasized nutrient-rich growth conditions. Of note, however, are the set of genes that become essential when bacteria are grown under nutrient stress. For example, more than 100 genes become indispensable when the...

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Autores principales:	Jean-Philippe Côté, Shawn French, Sebastian S. Gehrke, Craig R. MacNair, Chand S. Mangat, Amrita Bharat, Eric D. Brown
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3b569e9d707e47968807401b6c2f2035
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spelling	oai:doaj.org-article:3b569e9d707e47968807401b6c2f20352021-11-15T15:50:15ZThe Genome-Wide Interaction Network of Nutrient Stress Genes in <named-content content-type="genus-species">Escherichia coli</named-content>10.1128/mBio.01714-162150-7511https://doaj.org/article/3b569e9d707e47968807401b6c2f20352016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01714-16https://doaj.org/toc/2150-7511ABSTRACT Conventional efforts to describe essential genes in bacteria have typically emphasized nutrient-rich growth conditions. Of note, however, are the set of genes that become essential when bacteria are grown under nutrient stress. For example, more than 100 genes become indispensable when the model bacterium Escherichia coli is grown on nutrient-limited media, and many of these nutrient stress genes have also been shown to be important for the growth of various bacterial pathogens in vivo. To better understand the genetic network that underpins nutrient stress in E. coli, we performed a genome-scale cross of strains harboring deletions in some 82 nutrient stress genes with the entire E. coli gene deletion collection (Keio) to create 315,400 double deletion mutants. An analysis of the growth of the resulting strains on rich microbiological media revealed an average of 23 synthetic sick or lethal genetic interactions for each nutrient stress gene, suggesting that the network defining nutrient stress is surprisingly complex. A vast majority of these interactions involved genes of unknown function or genes of unrelated pathways. The most profound synthetic lethal interactions were between nutrient acquisition and biosynthesis. Further, the interaction map reveals remarkable metabolic robustness in E. coli through pathway redundancies. In all, the genetic interaction network provides a powerful tool to mine and identify missing links in nutrient synthesis and to further characterize genes of unknown function in E. coli. Moreover, understanding of bacterial growth under nutrient stress could aid in the development of novel antibiotic discovery platforms. IMPORTANCE With the rise of antibiotic drug resistance, there is an urgent need for new antibacterial drugs. Here, we studied a group of genes that are essential for the growth of Escherichia coli under nutrient limitation, culture conditions that arguably better represent nutrient availability during an infection than rich microbiological media. Indeed, many such nutrient stress genes are essential for infection in a variety of pathogens. Thus, the respective proteins represent a pool of potential new targets for antibacterial drugs that have been largely unexplored. We have created all possible double deletion mutants through a genetic cross of nutrient stress genes and the E. coli deletion collection. An analysis of the growth of the resulting clones on rich media revealed a robust, dense, and complex network for nutrient acquisition and biosynthesis. Importantly, our data reveal new genetic connections to guide innovative approaches for the development of new antibacterial compounds targeting bacteria under nutrient stress.Jean-Philippe CôtéShawn FrenchSebastian S. GehrkeCraig R. MacNairChand S. MangatAmrita BharatEric D. BrownAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jean-Philippe Côté Shawn French Sebastian S. Gehrke Craig R. MacNair Chand S. Mangat Amrita Bharat Eric D. Brown The Genome-Wide Interaction Network of Nutrient Stress Genes in <named-content content-type="genus-species">Escherichia coli</named-content>
description	ABSTRACT Conventional efforts to describe essential genes in bacteria have typically emphasized nutrient-rich growth conditions. Of note, however, are the set of genes that become essential when bacteria are grown under nutrient stress. For example, more than 100 genes become indispensable when the model bacterium Escherichia coli is grown on nutrient-limited media, and many of these nutrient stress genes have also been shown to be important for the growth of various bacterial pathogens in vivo. To better understand the genetic network that underpins nutrient stress in E. coli, we performed a genome-scale cross of strains harboring deletions in some 82 nutrient stress genes with the entire E. coli gene deletion collection (Keio) to create 315,400 double deletion mutants. An analysis of the growth of the resulting strains on rich microbiological media revealed an average of 23 synthetic sick or lethal genetic interactions for each nutrient stress gene, suggesting that the network defining nutrient stress is surprisingly complex. A vast majority of these interactions involved genes of unknown function or genes of unrelated pathways. The most profound synthetic lethal interactions were between nutrient acquisition and biosynthesis. Further, the interaction map reveals remarkable metabolic robustness in E. coli through pathway redundancies. In all, the genetic interaction network provides a powerful tool to mine and identify missing links in nutrient synthesis and to further characterize genes of unknown function in E. coli. Moreover, understanding of bacterial growth under nutrient stress could aid in the development of novel antibiotic discovery platforms. IMPORTANCE With the rise of antibiotic drug resistance, there is an urgent need for new antibacterial drugs. Here, we studied a group of genes that are essential for the growth of Escherichia coli under nutrient limitation, culture conditions that arguably better represent nutrient availability during an infection than rich microbiological media. Indeed, many such nutrient stress genes are essential for infection in a variety of pathogens. Thus, the respective proteins represent a pool of potential new targets for antibacterial drugs that have been largely unexplored. We have created all possible double deletion mutants through a genetic cross of nutrient stress genes and the E. coli deletion collection. An analysis of the growth of the resulting clones on rich media revealed a robust, dense, and complex network for nutrient acquisition and biosynthesis. Importantly, our data reveal new genetic connections to guide innovative approaches for the development of new antibacterial compounds targeting bacteria under nutrient stress.
format	article
author	Jean-Philippe Côté Shawn French Sebastian S. Gehrke Craig R. MacNair Chand S. Mangat Amrita Bharat Eric D. Brown
author_facet	Jean-Philippe Côté Shawn French Sebastian S. Gehrke Craig R. MacNair Chand S. Mangat Amrita Bharat Eric D. Brown
author_sort	Jean-Philippe Côté
title	The Genome-Wide Interaction Network of Nutrient Stress Genes in <named-content content-type="genus-species">Escherichia coli</named-content>
title_short	The Genome-Wide Interaction Network of Nutrient Stress Genes in <named-content content-type="genus-species">Escherichia coli</named-content>
title_full	The Genome-Wide Interaction Network of Nutrient Stress Genes in <named-content content-type="genus-species">Escherichia coli</named-content>
title_fullStr	The Genome-Wide Interaction Network of Nutrient Stress Genes in <named-content content-type="genus-species">Escherichia coli</named-content>
title_full_unstemmed	The Genome-Wide Interaction Network of Nutrient Stress Genes in <named-content content-type="genus-species">Escherichia coli</named-content>
title_sort	genome-wide interaction network of nutrient stress genes in <named-content content-type="genus-species">escherichia coli</named-content>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/3b569e9d707e47968807401b6c2f2035
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The Genome-Wide Interaction Network of Nutrient Stress Genes in <named-content content-type="genus-species">Escherichia coli</named-content>

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