Controlling Pathogenic Gram-Negative Bacteria by Interfering with Their Biofilm Formation

Many bacteria start production of pathogenicity factors when organised in aggregates, so-called biofilms, where they are much more protected against toxic agents. To form biofilms bacteria monitor their cell density by a process called quorum sensing using small, water soluble molecules which act as autoinducers. N-acyl homoserine lactones (AHL) where the acyl side chains vary in length and degree of oxidation and 4,5-dihydroxy-2,3-pentanedion or furanosyl borate diester formed from ribose-homocysteine have been identified as autoinducers but more must exist. Plants and animals exposed to a wet environment developed several strategies to control biofilms and embedded pathogenic bacteria in particular. The red macroalgae Delisea pulchra is devoid of biofilms at its surface and produces a number of secondary metabolites with a furanone ring interfering with the action of AHL. Taking the lead structure from these metabolites and from AHL several smaller molecules have been developed, which prevent biofilm formation in many bacteria. In the review the different approaches to control bacterial biofilms will be described focussing on the progress made in the development of autoinducer antagonists and problems caused by their specificity and toxicity for the host. The combination with antibiotics and first applications in animal models will be discussed.