Biofilm Inhibition by Nanoparticles - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 375

formation has been the predominant mechanism of broad-spectrum tolerance.
Biofilm are complexes made up of microbes surrounded by a hydrated matrix that
is secreted by these indwelling microbes to protect or facilitate their growth in
hostile environments. Biofilms are characterized by their extracellular polymeric
substances (EPS) which contain polysaccharides, proteins, lipids, and nucleic acids.
Apart from conferring resistance to the inhabitants, biofilms also facilitate various
other functions like aggregation, retention of water and nutrients, absorption of
nutrients, protection against host immune responses, and horizontal gene transfer.
Studies have even suggested that the multicellular behavior of biofilm inhabitants is
similar to higher multicellular organisms.
In theory, antibiofilm agents are less likely to cause selective pressure for the
evolution of resistance because they do not kill pathogens as do antibiotics.
Successful antibiofilm agents can either inhibit the formation of biofilms or disrupt
mature biofilms. Antibiofilm agents are preferred over antibiotics in some instances
as they prevent or disrupt biofilms, facilitating their clearance by the host immune
system. Numerous sources from soil to sea and herbs to plants have been screened
for antibiofilm activity. Even, some antibiotics have been shown to possess
antibiofilm activity at sublethal concentrations. In addition, synthetic agents with
antibiofilm properties are of interest because of their feasibility and availability for
application.
Various agents such as synthetic chemicals, microbial secondary metabolites,
phenolic compounds and other phytochemicals from plants, antibiotics at their
sublethal concentrations, nucleases, proteases and other enzymes, peptides, etc.,
were shown to have the potential to inhibit biofilm formation and/or disrupt mature
biofilms. Numerous synthetic chemicals like thiazolidinone derivatives (Pan
et al. 2010 ; Rane et al. 2012 ), aminoimidazoles (Furlani et al. 2012 ), diazopyrazole
derivatives (Raimondi et al. 2012 ), bromopyrrole alkaloids (Rane et al. 2013 ), etc.,
were shown to have antibiofilm potential against Gram-positive bacterial pathogens
like Staphylococcus aureus , Streptococcus epidermidis , and Enterococcus faecalis .
Other synthetics like niclosamide (Imperi et al. 2013 ), esomeprazole (Singh
et al. 2012 ), chlorogenic acid (Karunanidhi et al. 2013 ), and zinc (Wu et al. 2013 )
showed promising results against various Gram negative bacteria, especially Pseu-
domonas aeruginosa . Other chemicals such as caspofungin (Bink et al. 2012 ) and
farnesol (Ramage et al. 2002 ) were shown to be active against the biofilms of
Candida albicans . Lastly, antibiotics at sublethal concentrations were shown to
inhibit biofilms, which is of interest, as these sublethal concentrations are less likely
to induce the development of resistance (Balaji et al. 2013 ; Gilbert et al. 2002 ;
Latimer et al. 2012 ).
Various microbial extracts (Bakkiyaraj and Pandian 2010 ; Bakkiyaraj
et al. 2012 ; Nithya et al. 2010b , 2011 ; Nithya and Pandian 2010 ) and their
secondary metabolites like usnic acid and atranorin (Pompilio et al. 2013 ), glyco-
lipid biosurfactants (Kiran et al. 2010 ), phenylacetic acid (Musthafa et al. 2012b ),
ophiobolins (Arai et al. 2013 ), and piperazinedione (Musthafa et al. 2012a ) were
reported to have antibiofilm properties against bacterial and fungal pathogens.
Apart from the microbial metabolites, enzymes were also shown to inhibit the