Staphylococcus aureus Biofilm Formation and Inhibition - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 232

Fig. 2 Quorum-sensing-mediated detachment of S. aureus biofilms. S. aureus biofilms were
grown for 2 days with a constitutive RFP expressing plasmid and an agr -controlled GFP plasmid.
AIP signal was added to the growth media and biofilm integrity and fluorescence were monitored
for 2 days (for further details, see Boles and Horswill 2008 ). In panel ( a ), AIP was added to a
S. aureus wild-type strain, and in panel ( b ) it was added to a ʔagr mutant strain. The images are

reconstructions of confocal microscopy pictures, and they show that the wild-type strain will
detach from the biofilm during quorum-sensing induction. Reprinted with permission from Boles
and Horswill ( 2008 )

epidermidis , the prevention of PSM expression limited dissemination using a

mouse model of foreign body infection (Wang et al. 2011b ). Altogether, these
results emphasize the significance of PSMs as modulators of biofilm development.
The other major class of molecules positively regulated by the agr system and
impacting biofilm development are the extracellular proteases. Numerous studies
have demonstrated that various regulatory conditions that lead to high extracellular
protease levels negatively impact S. aureus biofilm formation (Mootz et al. 2013 ;
Boles and Horswill 2011 ; Lauderdale et al. 2009 , 2010 ; O'neill et al. 2008 ; Marti
et al. 2010 ; Tsang et al. 2008 ; Zielinska et al. 2012 ). Most S. aureus strains secrete
at least ten proteases including a metalloprotease (Aur), seven serine proteases
(SspA and SplA-F), and two cysteine proteases (Staphopains ScpA and SspB). All
of these proteases are induced when RNAIII levels accumulate (Thoendel
et al. 2011 ), and not surprisingly, the deletion of all these proteases results in
increased abundance of secreted and surface-associated virulence factors (Kolar
et al. 2013 ). Several proteins with biofilm roles have been identified that are cleaved
by these core proteases. For instance, Aur metalloprotease cleaves surface-exposed
clumping factor ClfB (McAleese et al. 2001 ) and PSMs (Zielinska et al. 2011 ). The
increased stability of PSMs in an aur mutant leads to increased osteoblast cell death
and bone destruction in a murine model of osteomyelitis (Cassat et al. 2013 ). SspA
(V8) serine protease degrades the fibronectin-binding MSCRAMMs (McGavin
et al. 1997 ) as well as Protein A (Karlsson et al. 2001 ), and there is evidence that
SspA might be important in biofilm remodeling (McGavin et al. 1997 ; Marti

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