Disturbing the spatial structure of biofilms affects the expression of agr regulated virulence factors in Staphylococcus aureus

Staphylococcus aureus uses quorum sensing and nutrient
availability to control the expression of agr-regulated virulence
factors. Quorum sensing is mediated by autoinducing peptide
(AIP), which at high concentration, reduces expression of surface
attachment proteins (coa, fnbpA), and increases expression of
exotoxins (lukS) and proteases (splA). Nutrient availability can be sensed
through the saeS/saeR system. Low nutrients increase
expression of saeR, which augments expression
of coa and fnbpA distinct from
AIP. The formation of spatial structure, such as biofilms, can
alter quorum sensing and nutrient acquisition. In natural environments,
biofilms encounter forces that may alter their spatial structure. This may
impact quorum sensing and/or nutrient acquisition, and thus affect the
expression of agr-regulated virulence factors. However, this has
not been studied. We show that periodically disturbing biofilms composed
of S. aureus using a physical force affects the
expression of agr-regulated virulence factors. In nutrient-poor
environments, disturbance increased the expression of
coa, fnbpA, lukS, and splA. Disturbance into a
nutrient-rich environment at low or high disturbance amplitudes moderately
reduced expression of coa and fnbpA but
increased expression of lukS and splA.
Interestingly, at an intermediate amplitude, the overall expression
of agr-regulated virulence factors was the lowest; expression
of lukS and splA remained unchanged
relative to an undisturbed biofilm while expression
of coa and fnbpA significantly decreased. We
hypothesize that these changes are a result of disturbance-driven changes
in access to AIP and nutrients. Our results may allow the identification
of environments where virulence is enhanced, or reduced, owing to
disturbance.