## 5 Coating Materials with Embedded Antibiotics and Other Antibofilm Agents
### Biofilm Control by Inhibitors or Modulators of Bacterial Signaling Processes  
5.1 Antibioticfilm Coatings with Physically Entrapped or Covalently Immobilized Quorum Sensing Inhibitors  
The signal transfer interference approach is another promising strategy to control biofilm infections by interfering with bacterial cell-to-cell communication. By impairing quorum sensing (QS) systems, quorum sensing inhibitors (QSIs) may suppress biofilm formation on medical devices. [PERSON] et al. [51] prepared antibiofilm coatings on glass slides support by incorporating the QSI halogenated furanone compound (Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BBF) (Figure 5) into a Nafion polymer matrix.  
Figure 4: Chemical structure of usnic acid.  
The antib biofilm activity was tested on a mixed microbial culture and on three pure strains of _P. aeruginosa_, _E. coli_, and _Bacillus subtilis_. The best results were obtained for a coating prepared by immersing the glass slides support into a 1% Nafion solution that contained 10 mg/L BBF for 12 h. The extent of biofilm formation after various incubation times (6, 12, 24, 48, and 72 h) was indirectly determined using the crystal violet staining assay by measuring the optical density at 600 nm. Compared to uncoated control slides, the glass slides coated with 1% Nafion polymer and 10 mg/mL BBF (BBF-Nafion) showed a biofilm reduction of 51% for the mixed culture and between 23% and 48% depending on the type of the pathogen for the pure strain cultures after 48 h of incubation. The authors also proposed a possible mechanism to explain the synergetic effect on biofilm inhibition observed for the BBF-Nafion coatings compared to the coating with BBF or Nafion alone. They suggested that a large amount of sulfonic acid groups on Nafion are exposed on the outer surface of the composite BBF-Nafion coating, thereby creating a negatively charged surface that repels bacteria, while the active QSI, which is slowly released from the coating, binds to membrane-associated receptor proteins of bacterial cells, thereby impeding their interaction with the native autoinducer signaling molecules and inhibiting the expression of some functional genes.  
[PERSON] and co-workers [52] used the extremely versatile click chemistry techniques implying the copper-catalyzed 1,3-dipolar cycloaddition reaction between an azide and an alkyne to form a 1,2,3-triazole ring, which acts as a linker for the attachment of potent QS inhibitors dihydropyrrolones (DHPs) [53] to a glass substrate. Following the procedure exemplified in Scheme 10, the authors synthesized a series of glass substrate attached DHPs and assessed the antibiofilm activity of the functionalized substrates. They proved the ability of surface-attached DHPs to interfere with the QS-controlled transcription of the virulence gene _lasB_ in _P. aeruginosa_ in vitro. _LasB_ or pseudolysin is a multifunctional protease that, in the acute stage of _P. aeruginosa_ infections, degrades the constituents of the host extracellular matrix (ECM), namely elastin, collagen, fibronectin, laminin, and vitronectin provoking tissue injury and hemorrhage. During chronic infections, _lasB_ disables or dismantles aspects of the host immune response by degrading or inactivating several components of the immune system [54]. The authors reported a 72% repression of _lasB_ gene expression by surface attached DHPs with no affection for cell viability. Moreover, these surface-immobilized QS inhibitors reduced bacterial adhesion up to 97% for both _P. aeruginosa_ and _S. aureus_[52].  
Figure 5: Chemical structure of the quorum sensing inhibitor, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone.