# Biology and Regulation of Staphylococcusococcal Biofilm
## 10 Recent Attempts to Reduce/Destroy a Biofilm during Infection  
Dozens of recent papers described different attempts to reduce biofilm formation or to destroy an already-formed biofilm in order to avoid the removal or replacement of an implanted material. Enzymes, antimicrobial peptides, bacteriophages, and natural compounds from vegetal origins have been used, mainly in vitro, with variable results [133; 134; 135]. Interesting observations were reported by [PERSON] in the field of meat-chain production using natural compounds extracted from essential oils alone or in combination with EDTA [133]. The authors described a significant effect in terms of the antimicrobial capacity of thymol, limonene, geraniol, or eugenol and an important inhibition of the biofilm formation of _S. aureus_, _Enterococcus_, and _Pseudomonas_ when these molecules were used in combination with EDTA. A similar strategy of potentiation of biocides by EDTA was used successfully on an already-formed biofilm [140]. These strategies appeared to be more adapted to the treatment of surfaces or devices than to medical materials. Other natural molecules have been identified from human milk, such as oligosaccharides, that allow for an appreciable decrease in _S. aureus_ biofilm formation [136]. Other groups reported the efficacy of different synthetic molecules of an organic [134; 139] or peptidic [135] nature on biofilm formation with clear success. Impressive results were obtained using a non-toxic acyclic amine derivative that yielded an extensive reduction of a biofilm and bacterial count in a model of urinary catheter infection [139]. The hypotheses of these studies relied on the alteration of the regulation of the biosynthesis process of bacterial biofilm, especially through the inhibition of the quorum-sensing system, which is an appealing solution.  
Based on the observation that antibiotics alone have almost no effect on the destruction of already-formed biofilms, [PERSON] and colleagues combined various molecules to reduce the amount of biofilm and embedded bacteria on a material. The most impressive effect was observed with combinations of oxytetracycline and subtilisin A or oxytetracycline and calcium gluconate [146]. Divalent cations, such as Ca\({}^{2+}\),and proteins possibly have a significant role in the structuration of the extracellular matrix that constitutes a bacterial biofilm, and the combination of these compounds with oxytetracycline resulted in a synergistic effect of killing and detachment [146]. A similar synergism was observed when fusidic acid and the quaternary ammonium berberine chloride were used, even on fusidic-acid-resistant MRSA isolates [147]. An interesting study reported various effects of baicalein--an inhibitor of the cytochrome p450 system--on the alteration of toxin expression in _S. aureus_ and on biofilm formation [148]. The utilization of baicalein and vancomycin yielded a drastic reduction in biofilm formation and bacterial viability. The authors suggested a baicalein-mediated mechanism that yields the disruption of mature biofilms and increases the permeability of the bacterial envelope to antibiotics [148].  
Bacterial biofilms are composed mainly of polymeric molecules: DNA, polysaccharides, and proteins. Hydrolytic enzymes are also potentially interesting molecules. [PERSON] and colleagues obtained very interesting results by using an engineered endolysin treatment in vitro and in vivo in a skin model of infection. The authors obtained a complete disinfection of the contaminated sites after treatment [138]. Similar results were envisioned by using lytic bacteriophages on already-formed biofilms. A recent study by [PERSON] and colleagues illustrated nicely the potential of active phage particles. The authors obtained impressive results following a single treatment of already-formed biofilms for 24-96 h. These different attempts at biofilm eradication support the possible development of alternative strategies to antibiotics for the treatment of contaminated biomaterials used in a clinical context.