Transcriptional downregulation of agr expression in Staphylococcus aureus during growth in human serum can be overcome by constitutively active mutant forms of the sensor kinase AgrC

Title: Transcriptional downregulation of agr expression in Staphylococcus aureus during growth in human serum can be overcome by constitutively active mutant forms of the sensor kinase AgrC
Author(s): James, EH
Edwards, AM
Wigneshweraraj, S
Item Type: Journal Article
Abstract: The temporal and cell density-dependent regulation of expression of virtually all the Staphylococcus aureus virulon is under the control of the agr (accessory gene regulatory) operon. The expression of the agr operon is subject to transcriptional regulation by the AgrA/C two-component response regulator/sensor kinase pair. During bacteraemia, a frequent syndrome caused by methicillin-resistant S. aureus (MRSA), the transcriptional downregulation of agr expression has been attributed to the sequestration of the quorum-signalling molecule auto-inducing peptide (AIP) by the human serum component apolipoprotein B as part of an innate immune response to infection. However, it is not known whether transcriptional downregulation of agr expression during growth in human serum is additionally subjected to regulation by transcription regulatory proteins that either directly or indirectly affect transcription from the agr operon promoters. Here, using chromosomal fluorescence reporters of agr expression in S. aureus, we show that the transcriptional downregulation of agr expression in human serum can be overcome using constitutive active mutant forms of AgrC. Therefore, it seems that the sequestration of the AIP is likely to be the only mechanism by which the host innate immune response limits agr expression at the transcriptional level to maintain the host–pathogen balance towards a noninvasive outcome.
Publication Date: 1-Dec-2013
Date of Acceptance: 17-Oct-2013
URI: http://hdl.handle.net/10044/1/40109
DOI: http://dx.doi.org/10.1111/1574-6968.12309
ISSN: 0378-1097
Publisher: Oxford University Press
Start Page: 153
End Page: 162
Journal / Book Title: FEMS Microbiology Letters
Volume: 349
Issue: 2
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BB/I001492/1
Copyright Statement: © 2013 Federation of European Microbiological Societies. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/3.0/) which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Microbiology
MICROBIOLOGY
transcription regulation
GFP transcriptional reporters
two-component systems
INFECTIONS
INHIBITION
SYSTEMS
SARA
GFP transcriptional reporters
transcription regulation
two-component systems
Bacterial Proteins
Base Sequence
Gene Expression Regulation, Bacterial
Gene Order
Humans
Intracellular Space
Molecular Sequence Data
Mutation
Operon
Promoter Regions, Genetic
Protein Kinases
Serum
Staphylococcus aureus
Trans-Activators
Transcription, Genetic
Intracellular Space
Serum
Humans
Staphylococcus aureus
Protein Kinases
Bacterial Proteins
Trans-Activators
Transcription, Genetic
Gene Expression Regulation, Bacterial
Base Sequence
Gene Order
Mutation
Operon
Molecular Sequence Data
Promoter Regions, Genetic
Microbiology
06 Biological Sciences
11 Medical And Health Sciences
07 Agricultural And Veterinary Sciences
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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