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

• Published in: FEMS microbiology letters Vol. 349; no. 2; pp. 153 - 162
• Main Authors: James, Ellen H., Edwards, Andrew M., Wigneshweraraj, Sivaramesh
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2013; Wiley-Blackwell; Oxford University Press; John Wiley & Sons Ltd
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Base Sequence; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Bacterial; Gene Order; GFP transcriptional reporters; Humans; Immune response; Intracellular Space - metabolism; Microbiology; Miscellaneous; Molecular Sequence Data; Mutation; Operon; Promoter Regions, Genetic; Protein Kinases - genetics; Protein Kinases - metabolism; Research Letters; Serum; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - growth & development; Staphylococcus aureus - metabolism; Trans-Activators - chemistry; Trans-Activators - genetics; Trans-Activators - metabolism; transcription regulation; Transcription, Genetic; two‐component systems; GFP transcriptional reporters; transcription regulation; two-component systems; Human; Enzyme; Transferases; Regulation(control); Kinase; Bacteria; Micrococcales; Serum; Micrococcaceae; Mutation; Staphylococcus aureus
• ISSN: 0378-1097; 1574-6968; 1574-6968
• DOI: 10.1111/1574-6968.12309

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.