Going beyond the Control of Quorum-Sensing to Combat Biofilm Infections

Abstract

Most bacteria attach to surfaces where they form a biofilm, cells embedded in a complex matrix of polymers. Cells in biofilms are much better protected against noxious agents than free-living cells. As a consequence it is very difficult to control pathogens with antibiotics in biofilm infections and novel targets are urgently needed. One approach aims at the communication between cells to form and to maintain a biofilm, a process called quorum-sensing. Water soluble small-sized molecules mediate this process and a number of antagonists of these compounds have been found. In this review natural compounds and synthetic drugs which do not interfere with the classical quorum-sensing compounds are discussed. For some of these compounds the targets are still not known, but others interfere with the formation of exopolysaccharides, virulence factors, or cell wall synthesis or they start an internal program of biofilm dispersal. Some of their targets are more conserved among pathogens than the receptors for quorum sensing autoinducers mediating quorum-sensing, enabling a broader application of the drug. The broad spectrum of mechanisms, the diversity of bioactive compounds, their activity against several targets, and the conservation of some targets among bacterial pathogens are promising aspects for several clinical applications of this type of biofilm-controlling compound in the future.

Keywords: biofilm dispersal; biofilm infection; quorum sensing.

Figure 1

Some of the well studied autoinducers mediating quorum-sensing in bacteria and fungi.

Figure 2

Antagonist of autoinducers of quorum-sensing competing with acyl-homoserine lactones, autoinducer-2 or autoinducer peptides (AIP) of Staphylococcus aureus.

Figure 3

Structures of the Pseudomonas quinolone signal (PQS) 22 and two of its recently found inhibitors.

Figure 4

A number of bioactive cyclic dipeptides have been described; some of them also seem to have a role in quorum-sensing. From these compounds inhibitors have been developed. Many of these compounds mediate interspecies interactions.

Figure 5

Many cis-2-alkenoyl acids mediate the communication between different species but cis-2-decenoic acid has been found to trigger the process of biofilm dispersal in several species including Pseudomonas aeruginosa.

Figure 6

A number of natural products and their derivatives have been found to prevent the formation of biofilms or to disperse established ones but their mechanisms of action are still unknown.