Macauley J. Green
Modelled-Microgravity Reduces Virulence Factor Production in Staphylococcus aureus through Downregulation of agr-Dependent Quorum Sensing
Green, Macauley J.; Murray, Ewan J.; Williams, Paul; Ghaemmaghami, Amir M.; Aylott, Jonathan W.; Williams, Philip M.
Authors
Ewan J. Murray
PAUL WILLIAMS PAUL.WILLIAMS@NOTTINGHAM.AC.UK
Professor of Molecular Microbiology
Professor AMIR GHAEMMAGHAMI AMIR.GHAEMMAGHAMI@NOTTINGHAM.AC.UK
Professor of Immunology and Immuno- Bioengineering
JONATHAN AYLOTT JON.AYLOTT@NOTTINGHAM.AC.UK
Professor of Analytical Science
PHIL WILLIAMS PHIL.WILLIAMS@NOTTINGHAM.AC.UK
Professor of Biophysics
Abstract
Bacterial contamination during space missions is problematic for human health and damages filters and other vital support systems. Staphylococcus aureus is both a human commensal and an opportunistic pathogen that colonizes human tissues and causes acute and chronic infections. Virulence and colonization factors are positively and negatively regulated, respectively, by bacterial cell-to-cell communication (quorum sensing) via the agr (accessory gene regulator) system. When cultured under low-shear modelled microgravity conditions (LSMMG), S. aureus has been reported to maintain a colonization rather than a pathogenic phenotype. Here, we show that the modulation of agr expression via reduced production of autoinducing peptide (AIP) signal molecules was responsible for this behavior. In an LSMMG environment, the S. aureus strains JE2 (methicillin-resistant) and SH1000 (methicillin-sensitive) both exhibited reduced cytotoxicity towards the human leukemia monocytic cell line (THP-1) and increased fibronectin binding. Using S. aureus agrP3::lux reporter gene fusions and mass spectrometry to quantify the AIP concentrations, the activation of agr, which depends on the binding of AIP to the transcriptional regulator AgrC, was delayed in the strains with an intact autoinducible agr system. This was because AIP production was reduced under these growth conditions compared with the ground controls. Under LSMMG, S. aureus agrP3::lux reporter strains that cannot produce endogenous AIPs still responded to exogenous AIPs. Provision of exogenous AIPs to S. aureus USA300 during microgravity culture restored the cytotoxicity of culture supernatants for the THP-1 cells. These data suggest that microgravity does not affect AgrC-AIP interactions but more likely the generation of AIPs.
Citation
Green, M. J., Murray, E. J., Williams, P., Ghaemmaghami, A. M., Aylott, J. W., & Williams, P. M. (2023). Modelled-Microgravity Reduces Virulence Factor Production in Staphylococcus aureus through Downregulation of agr-Dependent Quorum Sensing. International Journal of Molecular Sciences, 24(21), Article 15997. https://doi.org/10.3390/ijms242115997
Journal Article Type | Article |
---|---|
Acceptance Date | Oct 27, 2023 |
Online Publication Date | Nov 6, 2023 |
Publication Date | 2023-11 |
Deposit Date | Nov 6, 2023 |
Publicly Available Date | Nov 9, 2023 |
Journal | International Journal of Molecular Sciences |
Print ISSN | 1661-6596 |
Electronic ISSN | 1422-0067 |
Publisher | MDPI |
Peer Reviewed | Peer Reviewed |
Volume | 24 |
Issue | 21 |
Article Number | 15997 |
DOI | https://doi.org/10.3390/ijms242115997 |
Keywords | astropharmacy; Staphylococcus aureus; agr; quorum sensing; autoinducing peptide; microgravity; virulence; colonization; rotating cell culture system |
Public URL | https://nottingham-repository.worktribe.com/output/27072774 |
Publisher URL | https://www.mdpi.com/1422-0067/24/21/15997 |
Files
Ijms-24-15997
(2.3 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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