Modelled-Microgravity Reduces Virulence Factor Production in through Downregulation of -Dependent Quorum Sensing.

Bacterial contamination during space missions is problematic for human health and damages filters and other vital support systems. 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 (accessory gene regulator) system. When cultured under low-shear modelled microgravity conditions (LSMMG), has been reported to maintain a colonization rather than a pathogenic phenotype. Here, we show that the modulation of expression via reduced production of autoinducing peptide (AIP) signal molecules was responsible for this behavior. In an LSMMG environment, the 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 reporter gene fusions and mass spectrometry to quantify the AIP concentrations, the activation of , which depends on the binding of AIP to the transcriptional regulator AgrC, was delayed in the strains with an intact autoinducible system. This was because AIP production was reduced under these growth conditions compared with the ground controls. Under LSMMG, reporter strains that cannot produce endogenous AIPs still responded to exogenous AIPs. Provision of exogenous AIPs to 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.