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32
et al., 2011). The purpose of this review is to present
those compounds derived from sponges that have
shown anti-biofilm potential without bactericidal effe-
cts, with particular focus on the screening and develo-
pment of our own che mical libraries as an example.
These non-lethal molecules are significant discoveries,
because they have the potential to serve as therapeutic
supplements that can enhance the efficiency of
conventional antibiotics against biofilm-based infecti-
ons without eliciting resistant phenotypes (Stowe et al.,
2011).
While it is important to continue to expand our
libraries of antibiotic molecules, it is essential for the
continued efficacy of all antimicrobial drugs that new
and effective adjuvants be discovered in or der to
mitigate the increasing microbial resistance derived
from biofilms (Stoodley et al., 2002).
1.1
Biofilm development and defense
Ever since van Leeuwenhoek noted his belief that the
number of or ganisms found in 17
th
century dental
plaque exceeded “the number of men in a kingdom”,
biofilms have been a part of our understanding of how
bacteria interact with their environment, but it was not
until the late 20
th
century that we began to realize their
true importance. Over t he last few deca des, intense
study of a deluge of bacterial species from diverse
environmental niches has lead to a generalized
conception of how biofilms are form ed (Stoodley et
al., 2002). For most species, biofilm formation occurs
in five distinct stages (Figure 1) that are defined by a
combination of phenotype and genetic changes (Stood-
ley et al., 2002). It is also during the first stage of
attachment that most antifouling and antimicrobial
compounds are the most effective, because the bacte-
ria have not coated themselves in t he exopolymeric
substance (EPS) and are in a vulnerable state (Stowe
et al., 2011).
Figure 1 Potent antifouling pyrrole-imidazole alkaloid natural
products: Oroidin (1), sceptrin (2), and bromoageliferin (3)
According to this theory, each biofilm contains a small
population of highly resistant bacteria that are able t o
survive antibiotic kill-off to re build the biofilm
population (Spoering and Lewis, 2001). Although the
concept of persist or cells has been around over
seventy years, it has only been through the recent
increase in medical biofilm research that the correla-
tion between biofilm-based disease relapse models
and persistor cells could have been made (Percival et
al., 2011). Since the persistor cells are protected, they
are able to reproduce once the microbicidal insult
abates and yield stronger progeny that have a significa-
ntly higher chance of being antibiotic resistant after
each treatment, leading to a chronic disease that is
driven by antibiotic resistant bacteria found in normal
acute infections (Stowe et al., 2011).
1.2
Anti-Biofilm agents derived from marine sponges
Marine sponges can be likened to little factories for
bioactive secondary metabolites. These benthic
organisms are so me of the sim plest multicellular
animals with litt le differentiation and long lives,
relying on the water around them to supply all their
essential needs. Therefore, the generation of chemical
defenses is a key element of their survival (Braekman
et al., 1992), whether they need to ward off predators,
fight off competition for space a nd resources or
control surface fouling (Pawlik, 1993). Sponges
utilize a plethora of chemical classes to protec t
themselves and even to communicate with symbiotic
organisms that can provide nutrients and additional
protection (Manzo et al., 2011). Many of t hese
chemicals have been found to have antifouling and
anti-biofilm properties, but very few have been shown
to modulate biofilm formation without killing the
bacteria or disrupting their growth. To date, only two
classes of marine sponge metabolites house
non-bactericidal biofilm modulators, the terpenoids
and the pyrrole-im idazoles (Melander et al., 2009).
Although not unique to sponges, one of the most
potent and diverse groups of molecules is the terpenes
and their derivatives.
1.3
Biofilm of medical implants
Because of the importance of bioactive compounds in
sponges to inhibit bacterial biofilm formation, in the
present study an attempt has been made to find out
catheter the extracts of the sponges
Aurora globostell-
ata
and
Spirastrella inconstans
var.
moeandrina Dendy