Staphylococcus aureus Biofilm Formation and Inhibition - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 237

6.1 Natural Product Inhibitors
As outlined in the preceding sections, many bacteria can produce agents that
prevent biofilm formation. In one recent example, D -tyrosine, D -phenylalanine,
and D -proline, as well as a mixture of D -amino acids, were shown to be effective
at inhibiting S. aureus biofilm formation (Kolodkin-Gal et al. 2010 ; Hochbaum
et al. 2011 ). One mechanism could be the improper incorporation of D -amino acids
in the peptidoglycan peptide side chains in the place of the terminal D -alanine. In
support of this proposal, the addition of D -alanine restored biofilm formation in the
presence of both D -tyrosine and the D -amino acid mixture. Additionally, biofilms
that were treated with D -amino acids were found to have fewer surface proteins
when compared to biofilms treated with L -amino acids by confocal microscopy
(Hochbaum et al. 2011 ). The anti-biofilm characteristics of D -amino acids are not
limited to S. aureus , as the authors found that D -amino acids also prevented biofilm
formation in other bacteria, such as Bacillus subtilis and Escherichia coli . Consid-
ering D -amino acids are produced in late biofilm cultures by B. subtilis , there may
be some general conserved nature to this biofilm dispersal strategy across bacterial
species.
In another recent example of a bacterial derived agent, the fatty acid messenger,
cis- 2-decanoic acid, was identified from culture supernatants of P. aeruginosa as
being broadly biofilm inhibitory (Davies and Marques 2009 ). The fatty acid
disrupted established biofilms across a large variety of bacterial species, including
S. aureus , and the authors postulated that it might function as a signaling molecule
in multispecies biofilms to induce dispersal in a synchronized manner. More
recently, cis- 2-decanoic acid has been shown to enhance the effectiveness of
antibiotics against S. aureus biofilms (Jennings et al. 2012 ). However, more work
is required to determine the specific mechanism through which biofilm degradation
occurs.
Plants are an abundant source of natural products and increasingly compounds
are being identified that are bioactive against S. aureus . Recently, ellagic acid
derivatives were identified from Rubus ulmifolius (Elmleaf blackberry) as being
anti-biofilm in nature (Quave et al. 2012 ). Ellagic acid prevented biofilm formation
in all lineages of S. aureus and enhanced the susceptibility of these biofilms to
antibiotics. Additionally, the ellagic acid bioactivity was effective on human
plasma conditioned surfaces to provide a more relevant mimic of the in vivo disease
state. At this time, preliminary studies suggest the anti-biofilm mechanism is not
through alteration of PIA production or inhibition of sarA expression (Quave
et al. 2012 ). More studies are needed to further define the ellagic acid mode of
action against S. aureus biofilms.
Tannic acid is another example of a plant-derived natural product that has
recently been shown to be anti-biofilm in nature (Lee et al. 2013 ; Payne
et al. 2013 ). In looking at the tannin-induced change in S. aureus extracellular
proteins, the immunodominant surface protein A (IsdA) increased in abundance. In
follow-up analysis, induced expression of the isdA gene was found to inhibit biofilm