Staphylococcus aureus Biofilm Formation and Inhibition - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 229

Fig. 1 Schematic of S. aureus biofilm development. Stage 1, a subpopulation of planktonic cells
lyse, release eDNA, and adhere to a conditioned surface using a combination of surface adhesins,
eDNA, and PIA. Stage 2, the attached cells grow to a microcolony that begins to display some
morphological features of a biofilm. Stage 3, the biomass accumulates and the structure matures
into an established biofilm that displays the expected characteristics, such as tower formation and
antimicrobial resistance. Stage 4, active (quorum-sensing) or mechanical mechanisms lead to
biofilm detachment and a return to the planktonic state. Multiple factors are involved in the
detachment phase, such as proteases and PSMs

the matrix composition varies across strain types and is highly dependent on the
environmental conditions promoting biofilm development. Much of the current
knowledge of the biofilm matrix is based on studies of enzymes or molecules that
destroy this cohesive material, and many of these matrix-degrading agents are
summarized in Table 1 .
The first extensively studied matrix component is the exopolysaccharide termed
PIA ( P olysaccharide I ntercellular A dhesin) or PNAG ( P oly N - A cetyl G lucosamine).
PIA is primarily composed of a 1-6 acetylglucosamine homopolymer, is partially

de-acetylated (15-20 %), and is negatively charged (Mack et al. 1996 ). It is
produced and secreted by the proteins encoded in the ica ( i nter c ellular a dhesion)
gene locus, icaADBC (Cramton et al. 1999 ), which include a N -acteylglucosamine
transferase (IcaA and IcaB) (Gerke et al. 1998 ), a predicted exporter (IcaC) (Gerke
et al. 1998 ), and a deacetylase (IcaD) (Vuong et al. 2004b ). This collection of
proteins builds the PIA polymer from UDP- N -acetylglucosamine to a structure that
is over 100 subunits in length. The ica locus is important for biofilm formation in
many S. aureus strains and expression is induced by a variety of environmental
conditions including low oxygen, glucose, osmolarity, temperature, and in the
presence of sub-inhibitory concentrations of antibiotics (Fitzpatrick et al. 2005 ;
Cramton et al. 2001 ). However, in a number of studies, S. aureus strains have been
identified that do not require the ica locus to generate a robust biofilm, and many of
these strains are clinical MRSA isolates (Beenken et al. 2003 ; Lauderdale
et al. 2010 ; Boles et al. 2010 ; Boles and Horswill 2008 ; O'neill et al. 2007 ).
The PIA-independent S. aureus strains rely on proteins and extracellular DNA
(eDNA) as the important components of the biofilm matrix. In the host, biofilm
development initiates with attachment to extracellular matrix material including
fibrinogen, fibronectin, and collagen, which coat foreign bodies (Francois
et al. 1998 , 2000 ). S. aureus possesses numerous surface-exposed MSCRAMMs
( M icrobial S urface C omponents R ecognizing A dhesive M atrix M olecules) as well

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