Cytolytic toxin production by Staphylococcus aureus is dependent upon the activity of the protoheme IX farnesyltransferase

Emily Stevens, Maisem Laabei, Stewart Gardner, Greg A Somerville, Ruth C. Massey

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Staphylococcus aureus is a medically important pathogen with an abundance of virulence factors that are necessary for survival within a host, including the production of cytolytic toxins. The regulation of toxin production is mediated by the Agr quorum sensing system, and a poorly defined post-exponential growth phase signal independent of Agr. As part of a recent genome wide association study (GWAS) to identify novel loci that alter the expression of cytolytic toxins, a polymorphism in the cyoE gene, which encodes a protoheme IX farnesyltransferase, was identified. This enzyme is essential for processing heme into the electron transport chain for use as an electron acceptor. Interestingly, without this enzyme S. aureus were repressed in their ability to secrete cytolytic toxins, and this appears to be mediated through repression of the Agr quorum sensing system. We hypothesize that the loss of electron transport is inducing feedback inhibition of metabolic capabilities that suppress the TCA cycle, and that this coupled with decreased RNAIII transcription prevents synthesis of cytolytic toxins.

Original languageEnglish (US)
Article number13744
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Farnesyltranstransferase
Quorum Sensing
Electron Transport
Heme
Staphylococcus aureus
Genome-Wide Association Study
Virulence Factors
Enzymes
Electrons
Growth
Genes
Staphylococcus aureus RNAIII

ASJC Scopus subject areas

  • General

Cite this

Cytolytic toxin production by Staphylococcus aureus is dependent upon the activity of the protoheme IX farnesyltransferase. / Stevens, Emily; Laabei, Maisem; Gardner, Stewart; Somerville, Greg A; Massey, Ruth C.

In: Scientific reports, Vol. 7, No. 1, 13744, 01.12.2017.

Research output: Contribution to journalArticle

@article{8df26ba731034008a6287c2af4a8fa1d,
title = "Cytolytic toxin production by Staphylococcus aureus is dependent upon the activity of the protoheme IX farnesyltransferase",
abstract = "Staphylococcus aureus is a medically important pathogen with an abundance of virulence factors that are necessary for survival within a host, including the production of cytolytic toxins. The regulation of toxin production is mediated by the Agr quorum sensing system, and a poorly defined post-exponential growth phase signal independent of Agr. As part of a recent genome wide association study (GWAS) to identify novel loci that alter the expression of cytolytic toxins, a polymorphism in the cyoE gene, which encodes a protoheme IX farnesyltransferase, was identified. This enzyme is essential for processing heme into the electron transport chain for use as an electron acceptor. Interestingly, without this enzyme S. aureus were repressed in their ability to secrete cytolytic toxins, and this appears to be mediated through repression of the Agr quorum sensing system. We hypothesize that the loss of electron transport is inducing feedback inhibition of metabolic capabilities that suppress the TCA cycle, and that this coupled with decreased RNAIII transcription prevents synthesis of cytolytic toxins.",
author = "Emily Stevens and Maisem Laabei and Stewart Gardner and Somerville, {Greg A} and Massey, {Ruth C.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-14110-8",
language = "English (US)",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Cytolytic toxin production by Staphylococcus aureus is dependent upon the activity of the protoheme IX farnesyltransferase

AU - Stevens, Emily

AU - Laabei, Maisem

AU - Gardner, Stewart

AU - Somerville, Greg A

AU - Massey, Ruth C.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Staphylococcus aureus is a medically important pathogen with an abundance of virulence factors that are necessary for survival within a host, including the production of cytolytic toxins. The regulation of toxin production is mediated by the Agr quorum sensing system, and a poorly defined post-exponential growth phase signal independent of Agr. As part of a recent genome wide association study (GWAS) to identify novel loci that alter the expression of cytolytic toxins, a polymorphism in the cyoE gene, which encodes a protoheme IX farnesyltransferase, was identified. This enzyme is essential for processing heme into the electron transport chain for use as an electron acceptor. Interestingly, without this enzyme S. aureus were repressed in their ability to secrete cytolytic toxins, and this appears to be mediated through repression of the Agr quorum sensing system. We hypothesize that the loss of electron transport is inducing feedback inhibition of metabolic capabilities that suppress the TCA cycle, and that this coupled with decreased RNAIII transcription prevents synthesis of cytolytic toxins.

AB - Staphylococcus aureus is a medically important pathogen with an abundance of virulence factors that are necessary for survival within a host, including the production of cytolytic toxins. The regulation of toxin production is mediated by the Agr quorum sensing system, and a poorly defined post-exponential growth phase signal independent of Agr. As part of a recent genome wide association study (GWAS) to identify novel loci that alter the expression of cytolytic toxins, a polymorphism in the cyoE gene, which encodes a protoheme IX farnesyltransferase, was identified. This enzyme is essential for processing heme into the electron transport chain for use as an electron acceptor. Interestingly, without this enzyme S. aureus were repressed in their ability to secrete cytolytic toxins, and this appears to be mediated through repression of the Agr quorum sensing system. We hypothesize that the loss of electron transport is inducing feedback inhibition of metabolic capabilities that suppress the TCA cycle, and that this coupled with decreased RNAIII transcription prevents synthesis of cytolytic toxins.

UR - http://www.scopus.com/inward/record.url?scp=85032207838&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032207838&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-14110-8

DO - 10.1038/s41598-017-14110-8

M3 - Article

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 13744

ER -