Staphylococcus aureus Biofilm Formation and Inhibition - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 238

formation and an isdA mutant was not sensitive to treatment, further suggesting the
tannic acid triggered increase in IsdA levels is the reason for the biofilm phenotype.
Tea is abundant in tannins and the exposure of S. aureus biofilms to tea replicated
these findings in vitro. Importantly, the authors also demonstrated that tannins were
anti-biofilm in vivo using a rat model of throat colonization (Payne et al. 2013 ).
IsdA is a lytic transglycosylase and could be modifying the S. aureus peptidoglycan
and altering biofilm development. Supporting this proposal, a catalytically inactive
form of IsdA had no effect on the biofilm capacity. However, the exact mechanism
of IsdA on biofilm limitation awaits further elucidation.
As another recent example of plant-derived compounds, magnolol, a major
component isolated from the stem bark of Magnolia species, has been demonstrated
to have anti-biofilm properties against S. aureus (Wang et al. 2011a ). Through
transcriptional profiling, it was shown that magnolol decreased cidA expression and
increased lrgAB expression, both loci with known connections to autolysis (Rice
and Bayles 2008 ). Supporting the profiling, magnolol treatment reduced S. aureus
autolysin activity in a dose-dependent manner (Wang et al. 2011a ), suggesting that
this natural product controls lysis and eDNA release, which is essential for
S. aureus biofilm formation (Rice et al. 2007 ).
Finally, there has been success from marine-derived natural products in identi-
fying anti-biofilm agents. Multiple reports have demonstrated that the
2-aminoimidazole motif found in the sponge-derived natural products oroidin and
related compounds are effective at preventing S. aureus and other bacterial patho-
gens from forming biofilms (Su et al. 2011 ; Stowe et al. 2011 ). These compounds
can synergize with antibiotics to increase the potency against MRSA biofilm
(Rogers et al. 2010 ). Interestingly, the 2-aminoimidazole scaffold might be func-
tioning as a biofilm inhibitor through a zinc chelation mechanism (Rogers
et al. 2009 ). There are critical S. aureus surface proteins, like SasG, that are
important for biofilm formation and require zinc to build a proper surface structure
(Gruszka et al. 2012 ; Conrady et al. 2008 ; Corrigan et al. 2007 ). Whether or not the
2-aminoimidazole containing compounds function through SasG inhibition mech-
anism or through another zinc-dependent process remains to be determined.
6.2 Synthetic Inhibitors
Some success has been achieved by screening combinatorial libraries for anti-
biofilm compounds. The aryl rhodamines are an interesting class of compounds
identified initially by screening against S. epidermidis biofilms and successfully
tested against other bacterial pathogens like S. aureus (Opperman et al. 2009 ).
These compounds are broadly anti-biofilm against a diverse array of clinical
S. aureus isolates in the low micromolar range, and they retain some activity against
other Gram-positive pathogens. The aryl rhodamines inhibit attachment of
S. aureus to surfaces, although the exact mechanism of action is not yet clear.