Staphylococcus aureus Biofilm Formation and Inhibition - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 234

5.2 Nuclease and Other DNases

The first identified and probably best studied S. aureus enzyme is nuclease (Nuc).
Nuc is a potent, secreted endonuclease that can degrade single- and double-stranded
DNA, as well as RNA, in a calcium-dependent manner (Cunningham et al. 1956 ;
Cuatrecasas et al. 1967 ). Although nuc gene expression was originally thought to be
part of the agr regulon, recent studies have shown it is controlled by the SaeRS
two-component system (Olson et al. 2013b ). Exogenous treatment of Nuc enzyme,
or controlled expression of nuc , prevents S. aureus biofilm formation (Kiedrowski
et al. 2011 ). S. aureus mutants lacking nuc produce larger biofilms compared to
wild-type strains due to accumulation of high MW eDNA, and this phenotype is
conserved across S. aureus strain types (Kiedrowski et al. 2011 ). In addition to the
S. aureus Nuc, other DNases have been shown to prevent S. aureus biofilm
formation on diverse abiotic surfaces, such as glass, titanium, and plastic
(Lauderdale et al. 2010 ; Izano et al. 2008 ; Mann et al. 2009 ).

5.3 Hyaluronate Lyase

β

Hyaluronate lyases are secreted bacterial enzymes that cleave the -1,4 glycosidic

bond of hyaluronic acid, a host matrix polymer (Hynes and Walton 2000 ). The
S. aureus hyaluronate lyase, encoded by the gene hysA , was initially described as a
“spreading factor” for its ability to promote infection dissemination in a murine
skin infection model (Duran-Reynals 1933 ). More recently, it has been demon-
strated that many S. aureus strains contain multiple forms of this enzyme (Hart
et al. 2013 ). The abundance of hyaluronic acid in the mammalian host, particularly
at in vivo biofilm infection sites (Jiang et al. 2011 ; Laurent and Fraser 1992 ), makes
it a potential component of the biofilm matrix in vivo. Recent studies in our
laboratory have found that there is increased biofilm formation in the presence of
hyaluronic acid in a MRSA hysA mutant, and exogenous addition of purified HysA
reduced biofilm formation (Rosenthal and Horswill, unpublished observations).
Along these lines, the Streptococcus intermedius hyaluronate lyase was shown to
be important for biofilm dispersal (Pecharki et al. 2008 ). These findings suggest that
the role of hyaluronate lyase in S. aureus biofilm dispersal warrants further
investigation.

5.4 Dispersin B

Dispersin B is an enzyme produced by the dental pathogen Actinobacillus
actinomycetemcomitans that has been shown to function as a N -acetyl-
glucosaminidase. When added exogenously to staphylococcal biofilms, the enzyme