Modelled-Microgravity Reduces Virulence Factor Production in <i>Staphylococcus aureus</i> through Downregulation of <i>agr</i>-Dependent Quorum Sensing
Bacterial contamination during space missions is problematic for human health and damages filters and other vital support systems. <i>Staphylococcus aureus</i> is both a human commensal and an opportunistic pathogen that colonizes human tissues and causes acute and chronic infections. Vi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/21/15997 |
| Summary: | Bacterial contamination during space missions is problematic for human health and damages filters and other vital support systems. <i>Staphylococcus aureus</i> 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 <i>agr</i> (accessory gene regulator) system. When cultured under low-shear modelled microgravity conditions (LSMMG), <i>S. aureus</i> has been reported to maintain a colonization rather than a pathogenic phenotype. Here, we show that the modulation of <i>agr</i> expression via reduced production of autoinducing peptide (AIP) signal molecules was responsible for this behavior. In an LSMMG environment, the <i>S. aureus</i> 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 <i>S. aureus agrP3::lux</i> reporter gene fusions and mass spectrometry to quantify the AIP concentrations, the activation of <i>agr</i>, which depends on the binding of AIP to the transcriptional regulator AgrC, was delayed in the strains with an intact autoinducible <i>agr</i> system. This was because AIP production was reduced under these growth conditions compared with the ground controls. Under LSMMG, <i>S. aureus agrP3::lux</i> reporter strains that cannot produce endogenous AIPs still responded to exogenous AIPs. Provision of exogenous AIPs to <i>S. aureus</i> 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. |
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| ISSN: | 1661-6596 1422-0067 |