## 2 Characterization of Bacterial Biofilms
### Alternative Strategies for Combating Bacterial biofilms
Importantly, these small molecules are highly efficacious, are generally nontoxic for mammalian cells, and show broad-spectrum antibacterial activity via employment of sophisticated and dynamic mechanisms of action [66; 67; 68]. Moreover, HDPs are able to effective combat biofilms because of their ability to penetrate, derange, and disperse biofilm structures [69]. One of the best-characterized representatives of natural HDPs is the human defense peptide LL-37 that affected biofilm formation of _P. aeruginosa_[70]. On the other hand, the following molecules belong to the group of synthetic peptides with efficient antibiofilm activity: peptide 1037 (LL-37 derivative), peptide 1018 (bactencin derivative), NRC16 (pleurocidin derivative), P10 (P60.4 Ac derivative), a hybrid peptide CAMA (ecropin-A and melittin-A derivative), and others [64]. Furthermore, some HDPs synergize with the action of antibiotics, which leads to the repression of molecular pathways regulating biofilm development [64; 69]. This kind of combinatorial approach, based on antimicrobial peptides and conventional antibiotics, has been applied successfully against biofilms formed by _P. aeruginosa_, _E. coli, A. baumannii, K. pneumoniae, S. enterica_, and methicillin-resistant _S. aureus_[64]. Additionally, such combination therapy is also applicable to biomedicine, an example of which is the synergistic effect of cryptic peptides of human apolipoprotein B and ciprofloxacin against _Pseudomonas_ and _Burkholderia_ strains, clinically isolated from patients with cystic fibrosis [68]. It is worth emphasizing that the greatest advantage of this combination therapy is the reduction of the selective pressure for the development of drug resistance, as it decreases concentrations of both used agents, i.e., peptides and antibiotics [64; 68]. The role of QS in biofilm formation has been demonstrated in many bacterial species. These systems influence the heterogeneous architecture of bacterial biofilms in the regulation of the synthesis of the degradative enzymes. QS may also regulate the antibiotic susceptibility by increasing antibiotic tolerance in bacterial biofilms [65]. Interestingly, QS deficiency can be associated with the formation of thinner biofilm layers and lower EPS production, which leads to the kanamycin sensitivity of biofilms of _P. aeruginosa_[71; 72]. Consequently, QS is considered a promising target for new antibiofilm agents. Moreover, QS inhibitors (enzymes and auto-inducing peptides) or RNA-III-inhibiting peptides [65], halogenated furanone compounds [73], quercetin [74], curcumin [33], and even ginseng extract or garlic extract [75; 76] contribute to overcoming the bacterial resistance in biofilm. Antimicrobial peptides that can inhibit bacterial cell division, such as pyrroloricin or microcin B17, also belong to the group of anti-biofilm agents. Pyrrhhocorcini is capable of binding with the multi-helical lid region of the bacterial heat-shock protein DnaK, and it interferes with the initiation step of DNA replication. Additionally, pyrrhocorcin takes part in the interaction between DnaK and DnaJ that causes cell death. This proline-rich antibacterial peptide is also responsible for disrupting the translation process by binding to the tunnel of the ribosome. Interestingly, microcin B17 may also inhibit the replication process of bacterial DNA by interacting with DNA gyrase [33]. Interestingly, [PERSON] and coworkers identified a group of structurally related materials comprising ester and cyclic hydrocarbon moieties that are able to reduce the attachment of pathogenic bacteria, such as _P. aeruginosa_, _S. aureus_, and _E. coli_[12; 77]. Importantly, this bacterial-material interaction is strictly dependent on surface chemistry and can be related to the individual cells sensing the nature of the polymer surface via sensory proteins of the bacterial envelope or a specific surface structure such as flagella and pili.