Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA

Eun-Jin Lee, Eduardo A. Groisman

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The facultative intracellular pathogen Salmonella enterica resides within a membrane-bound compartment inside macrophages. This compartment must be acidified for Salmonella to survive within macrophages, possibly because acidic pH promotes expression of Salmonella virulence proteins. We reasoned that Salmonella might sense its surroundings have turned acidic not only upon protonation of the extracytoplasmic domain of a protein sensor but also by an increase in cytosolic ATP levels, because conditions that enhance the proton gradient across the bacterial inner membrane stimulate ATP synthesis. Here we report that an increase in cytosolic ATP promotes transcription of the coding region for the virulence gene mgtC, which is the most highly induced horizontally acquired gene when Salmonella is inside macrophages. This transcript is induced both upon media acidification and by physiological conditions that increase ATP levels independently of acidification. ATP is sensed by the coupling/uncoupling of transcription of the unusually long mgtC leader messenger RNA and translation of a short open reading frame located in this region. A mutation in the mgtC leader messenger RNA that eliminates the response to ATP hinders mgtC expression inside macrophages and attenuates Salmonella virulence in mice. Our results define a singular example of an ATP-sensing leader messenger RNA. Moreover, they indicate that pathogens can interpret extracellular cues by the impact they have on cellular metabolites.

Original languageEnglish
Pages (from-to)271-275
Number of pages5
JournalNature
Volume486
Issue number7402
DOIs
Publication statusPublished - 2012 Jun 14
Externally publishedYes

Fingerprint

Salmonella
Virulence
Adenosine Triphosphate
Messenger RNA
Macrophages
Salmonella enterica
Membranes
Open Reading Frames
Genes
Cues
Protons
Mutation
Proteins

ASJC Scopus subject areas

  • General

Cite this

Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA. / Lee, Eun-Jin; Groisman, Eduardo A.

In: Nature, Vol. 486, No. 7402, 14.06.2012, p. 271-275.

Research output: Contribution to journalArticle

Lee, Eun-Jin ; Groisman, Eduardo A. / Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA. In: Nature. 2012 ; Vol. 486, No. 7402. pp. 271-275.
@article{4ca17dc9ce48465ea709e8ec5ca9c2c2,
title = "Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA",
abstract = "The facultative intracellular pathogen Salmonella enterica resides within a membrane-bound compartment inside macrophages. This compartment must be acidified for Salmonella to survive within macrophages, possibly because acidic pH promotes expression of Salmonella virulence proteins. We reasoned that Salmonella might sense its surroundings have turned acidic not only upon protonation of the extracytoplasmic domain of a protein sensor but also by an increase in cytosolic ATP levels, because conditions that enhance the proton gradient across the bacterial inner membrane stimulate ATP synthesis. Here we report that an increase in cytosolic ATP promotes transcription of the coding region for the virulence gene mgtC, which is the most highly induced horizontally acquired gene when Salmonella is inside macrophages. This transcript is induced both upon media acidification and by physiological conditions that increase ATP levels independently of acidification. ATP is sensed by the coupling/uncoupling of transcription of the unusually long mgtC leader messenger RNA and translation of a short open reading frame located in this region. A mutation in the mgtC leader messenger RNA that eliminates the response to ATP hinders mgtC expression inside macrophages and attenuates Salmonella virulence in mice. Our results define a singular example of an ATP-sensing leader messenger RNA. Moreover, they indicate that pathogens can interpret extracellular cues by the impact they have on cellular metabolites.",
author = "Eun-Jin Lee and Groisman, {Eduardo A.}",
year = "2012",
month = "6",
day = "14",
doi = "10.1038/nature11090",
language = "English",
volume = "486",
pages = "271--275",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "7402",

}

TY - JOUR

T1 - Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA

AU - Lee, Eun-Jin

AU - Groisman, Eduardo A.

PY - 2012/6/14

Y1 - 2012/6/14

N2 - The facultative intracellular pathogen Salmonella enterica resides within a membrane-bound compartment inside macrophages. This compartment must be acidified for Salmonella to survive within macrophages, possibly because acidic pH promotes expression of Salmonella virulence proteins. We reasoned that Salmonella might sense its surroundings have turned acidic not only upon protonation of the extracytoplasmic domain of a protein sensor but also by an increase in cytosolic ATP levels, because conditions that enhance the proton gradient across the bacterial inner membrane stimulate ATP synthesis. Here we report that an increase in cytosolic ATP promotes transcription of the coding region for the virulence gene mgtC, which is the most highly induced horizontally acquired gene when Salmonella is inside macrophages. This transcript is induced both upon media acidification and by physiological conditions that increase ATP levels independently of acidification. ATP is sensed by the coupling/uncoupling of transcription of the unusually long mgtC leader messenger RNA and translation of a short open reading frame located in this region. A mutation in the mgtC leader messenger RNA that eliminates the response to ATP hinders mgtC expression inside macrophages and attenuates Salmonella virulence in mice. Our results define a singular example of an ATP-sensing leader messenger RNA. Moreover, they indicate that pathogens can interpret extracellular cues by the impact they have on cellular metabolites.

AB - The facultative intracellular pathogen Salmonella enterica resides within a membrane-bound compartment inside macrophages. This compartment must be acidified for Salmonella to survive within macrophages, possibly because acidic pH promotes expression of Salmonella virulence proteins. We reasoned that Salmonella might sense its surroundings have turned acidic not only upon protonation of the extracytoplasmic domain of a protein sensor but also by an increase in cytosolic ATP levels, because conditions that enhance the proton gradient across the bacterial inner membrane stimulate ATP synthesis. Here we report that an increase in cytosolic ATP promotes transcription of the coding region for the virulence gene mgtC, which is the most highly induced horizontally acquired gene when Salmonella is inside macrophages. This transcript is induced both upon media acidification and by physiological conditions that increase ATP levels independently of acidification. ATP is sensed by the coupling/uncoupling of transcription of the unusually long mgtC leader messenger RNA and translation of a short open reading frame located in this region. A mutation in the mgtC leader messenger RNA that eliminates the response to ATP hinders mgtC expression inside macrophages and attenuates Salmonella virulence in mice. Our results define a singular example of an ATP-sensing leader messenger RNA. Moreover, they indicate that pathogens can interpret extracellular cues by the impact they have on cellular metabolites.

UR - http://www.scopus.com/inward/record.url?scp=84862273668&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862273668&partnerID=8YFLogxK

U2 - 10.1038/nature11090

DO - 10.1038/nature11090

M3 - Article

C2 - 22699622

AN - SCOPUS:84862273668

VL - 486

SP - 271

EP - 275

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 7402

ER -