Current and Emergent Control Strategies for Medical Biofilms - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 138

demonstrated Candida biofilm disrupting ability by di-rhamnolipid (RL-2) pro-
duced by P. aeruginosa DSVP20.
The antibiofilm activity of a glycolipid biosurfactant isolated from the marine
actinobacterium Brevibacterium casei MSA19 was evaluated by Kiran et al. ( 2010 )
against pathogenic biofilms in vitro. The disruption of the biofilm by the MSA19
glycolipid was consistent against mixed pathogenic biofilm bacteria. Therefore, it
could be suggested that the glycolipid biosurfactant can be used as a lead compound
for the development of novel antibiofilm agents.
Janek et al. ( 2012 ) have recently identified a biosurfactant, Pseudofactin II,
secreted by Pseudomonas fluorescens BD5, the strain obtained from freshwater
from the Arctic Archipelago of Svalbard. Pseudofactin II showed anti-adhesive
activity against several pathogenic microorganisms ( E. coli , E. faecalis , Entero-
coccus hirae , S. epidermidis , P. mirabilis , and two C. albicans strains), which are
potential biofilm formers on catheters, implants, and internal prostheses. Up to
99 % prevention was achieved by 0.5 mg/mL pseudofactin II. In addition,
pseudofactin II dispersed preformed biofilms. Pseudofactin II can be used as a
disinfectant or surface coating agent against microbial colonization of different
surfaces, e.g., implants or urethral catheters.
An overview of all the above-discussed strategies to control biofilms is given in
Fig. 5 . The targets of each approaches at different stages of biofilms and their
interrelation are depicted.
4.6 Small Molecule Control of Biofilms
Given the prominence of biofilms in infectious diseases, there has been an increased
effort toward the development of small molecules that inhibit and/or disperse
bacterial biofilms through non-microbicidal mechanisms. It will be meaningful to
distinguish molecules that have the ability to affect biofilm development via
non-microbicidal mechanisms, as the pressure on bacteria or fungi to evolve
resistance to these agents will be significantly reduced or even eliminated
(Worthington et al. 2012 ). Due to the scarcity of known molecular scaffolds that
inhibit/disperse bacterial biofilms, high throughput screening (HTS) has been
employed in attempts to discover leads for new anti-biofilm modulators. Here, we
have briefly summarized the application of chemical databases for the discovery of
lead small molecules, using HTS approaches, which mediate biofilm development.
These approaches are grouped into three steps:
1. The identification and development of small molecules that target one of the
bacterial signaling pathways involved in biofilm regulation
2. Chemical library screening for compounds with antibiofilm activity
3. The identification of natural products that possess antibiofilm activity, and the
chemical manipulation of these natural products to obtain analogues (using
structure activity relationship (SAR) method) with increased activity.