Biofilms are responsible for an estimated three quarters of all microbial infections. Now, inspired by marine natural product oroidin, American scientists have developed compounds that could help fight these colonies of bacteria.

Microbes in biofilm form behave differently from those that are free-floating. This can make them up to a thousand times more resistant to antibiotics and immune systems, and so biofilms difficult to disperse once formed. Yet biofilms are ubiquitous and, as well as being a threat to health, can cause agricultural and engineering problems. 'Probably the biggest challenge facing this area,' explained Christian Melander from the research team at North Carolina State University, in Raleigh, US, 'is the lack of molecular architecture that has been identified to inhibit and disperse bacterial biofilms.'

Oroidin's (left) amide bond is reversed in analogues (right) that can disperse bacterial films

Oroidin's documented activity against biofilm formation, together with its relatively simple structure, made it ideal for exploiting in the search for such scaffolds. Melander's team decided to reverse oroidin's amide bond, allowing easier analogue synthesis and the use of widely available amines to introduce diversity.

They found that some analogues were significantly better than oroidin at inhibiting biofilm formation in two strains of the pathogen Pseudomonas aeruginosa. The most active compound, a linear alkyl chain amide, was also able to disperse established biofilms.

According to Helen Blackwell, who carries out anti-biofilm research at the University of Wisconsin-Madison, US, these compounds are notable 'as they not only inhibit biofilm formation, but also are capable of dispersing preformed biofilms'. She added, 'this dispersion ability bodes well for this compound class for a number of biomedical and industrial applications.'
 

The group is now looking at further varying the most active amide's alkyl chain and also at removing the amide group entirely, as well as testing the compounds against other bacterial strains. Melander said that 'the ultimate goal is to be able to produce non-toxic compounds that are active in vivo.' 

Frances Galvin