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the development of biofilm related infections. 19 This high prevalence of biofilm
related infections is particularly problematic given the fact that bacteria in biofilms
can be up to 1000-fold more resistant to antibiotics. 23 In industry, biofilms have been
implicated e.g. in the contamination of installations in food industry, mild steel
corrosion, decreased passage through pipelines by colonization of the interior of the
pipes, and enhanced resistance of vessels by initiation of “biofouling” on the vessel
hulls. The yearly economic loss caused by ‘biofouling’ in the marine industry is
estimated at $ 6.5 billion. 24
One way to deal with this problem is the development of small molecules that are able
to prevent or destroy biofilm formation 25 . Only a few molecular scaffolds have been
identified to date, among which the best-studied examples are (1) the halogenated
furanones, which were originally isolated from the seaweed Delisea pulchra, 26-27 (2)
analogues of the homoserine lactone signalling molecules 28 and (3) analogues of the
sponge-derived marine natural alkaloids oroidin and bromoageliferin. 29-36 A
particularly valuable approach is the development of small molecules that specifically
target the biofilm formation in a non-toxic manner, as it is expected that resistance
against these compounds will emerge much slower than against classical
microbiocidal compounds. As a consequence, non-toxic biofilm inhibitors have the
potential to be used in a preventive treatment of a wide diversity of industrial and
medical surfaces. Furthermore, the potential to co-dose biofilm inhibitors and
classical antibiotics for the treatment of biofilm infections is also an attractive
option. 27
Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa are two well
studied organisms in terms of biofilm formation. Salmonella enterica is worldwide
one of the most important causes of foodborne infections. Salmonella is able to form
biofilms on a variety of both biotic surfaces (such as gallstones, 37 plant surfaces, 38-39
and epithelial cell layers 40 ) and abiotic surfaces (such as concrete, plastics, glass,
polystyrene, … ) 41-42 . These biofilms are an important survival strategy in all stages
of infection, from transmission to chronic infection. Severe non-typhoid Salmonella
infections are commonly treated with fluoroquinolones and third-generation
cephalosporins. Unfortunately, there are alarming reports concerning the development
of resistance against these antibiotics 43 , underlining the urgent need of alternative
anti-Salmonella strategies. Given the importance of biofilms in the spread of
Salmonella, the development of Salmonella biofilm inhibitors seems a promising