# Novel Approaches to Combat Medical Device-Associated BioFilms
## 3 Novel Approaches to Combat Medical Device-Associated Biofilms
### Antimicrobial Peptides
The main role of B22 has been shown to be the induction of ROS production, which destroys bacterial molecules, resulting in slowed cell growth or death [172]. LL-37 can downregulate the expression of the biofilm-related genes rhlA and rhlB, inhibit the synthesis of rhamntransferases, reduce biofilm formation, and degrade existing biofilms formed by _P. aeruginosa_[173]. In addition, LL-37 also has antibacterial effects on biofilms formed by other pathogens. The anti-biofilm effects and mechanisms of LL-37 and LL-37 derivatives against biofilms formed by different pathogens (such as _S. epidermidis, E. coli, S. aureus, C. albicans, and A. baumannii_) have been well-summarized by [PERSON] and other colleagues [1]. HBD3 and HBD3-derived peptides interfere with the expression of the adhesin gene and reduce the expression of adhesion proteins, which leads to a decrease in biofilm formation [174; 175]. In vivo, HBD3 has also been demonstrated to inhibit _Staphylococcus_ biofilm formation [176]. HBD3 and its derivatives are most commonly used to study anti-biofilm activity, and other defensins have also shown anti-biofilm activity in some studies. For example, HBD2 can inhibit _P. aeruginosa_ biofilm formation independent of biofilm regulatory pathways [177]. HNP-1 derivatives can also inhibit and eradicate the biofilm formation of multidrug-resistant uropathogenic _E. coli_, which may be used as a potential source for the treatment of biofilm-associated bacterial diseases [178]. The peptide Nal-P-113 inhibits _Porphyomonas gingivalis_ biofilm formation by inhibiting the synthesis of ATP-binding cassette (ABC) transporters and ATP-binding proteins [24; 179]. ABC transporters play a role in the cell adhesion phase of biofilm formation [180]. Temporin L (TL), derived from frog skin, has been confirmed to have antibiofilm activity [181]. It has been shown to act on the bacterial FtsZ protein, which is a protein involved in Z-ring formation, to inhibit cell division, thereby slowing bacterial growth [182]. Some AMPs can inhibit microbial cell adhesion or disperse cellular aggregates in the early stages of biofilm formation. LL-37 can also promote twitching in _P. aeruginosa_ and cause the bacteria to move instead of forming biofilms [173; 183]. Twitching is a form of surface motility that is regulated by type IV pili [184]. In _S. aureus_, IL-37- and LL-37-derived peptides have also been proven to inhibit the formation and degradation of existing biofilms [185]. In _P. aeruginosa_, the antibiofilm peptide 1037 can also directly inhibit biofilms by reducing swimming and swarming motilities, stimulating twitching motility, and suppressing the expression of a variety of genes involved in biofilm formation [186]. Polymyxin B (PmB), which is a cationic bacterial AMP produced by _Bacillus polymyxa_, can affect _V. cholerae_ flagella, resulting in a decrease in motility and a compromised ability to form biofilms [187]. The formation of biofilms can also be inhibited by interruption of the signaling system of bacterial cells. QS is a cell-cell communication process that regulates multiple physiological and biochemical functions [1]. The human cathelcidin AMP LL-37 can prevent biofilm formation by inhibiting QS in microorganisms [183]. The immunomodulatory peptide innate defense regulator (IDR)-1018 was able to potently prevent biofilm formation and eradicate preformed biofilms formed by diverse species of Gram-negative bacteria and the Gram-positive bacterium _S. aureus_ by blocking (p)ppGpp and signaling nucleotides [188]. Persister cells are a small subgroup of bacterial cells that are in a dormant state and are highly resistant to antibiotics. Some AMPs can prevent the formation of biofilms and promote the degradation of biofilms by interfering with the formation of persister cells [189]. The representative AMP is SAAP-148. _S. aureus_, which survives under the action of high-dose rifampicin, can be completely cleared within 2 h by low concentrations of SAAP-1448 [190].