**2.2 Control of the global regulators**

Beside the QS regulons, other global regulators exhibit crucial functions in dominating the expression of various genes in assortment style as a response to environmental stimuli and changes, most notably the temperature change [5]. These so-called global regulators enable the bacterial communities to survive different environmental stresses including starvations, pH changes and temperature fluctuations, through the quick conformation of bacterial physiology and structure [79].

Among many regulators that coordinate gene expression in bacteria, in Gramnegative bacteria, the global regulator termed histone-like nucleoid-structuring (H-NS) protein is relatively significant and of paramount importance [80]. H-NS has been considered as the main model of studying how global regulators can affect bacterial structure and physiology. The H-NS protein is incorporated in the regulation of many genes responsible for controlling the physiological functions of Gram-negative bacterial cells involving cellular functions, survival under different environmental conditions and production of various virulence factors [81, 82]. Moreover, in Gram-positive bacteria, there are several global regulatory loci [83]. Among them in the *S. aureus*, SarA, a regulatory DNA binding protein involved in controlling the virulence genes expression, is well documented [84]. During regulation of the expression of various genes, these regulators have been demonstrated to act either as a positive regulators through enhancing the stability of the mRNA of expressed genes, resulting in excessive translation, or as a silencer protein that alter and decrease the gene expression by hindering binding of RNA polymerases to the promoters of target genes [85, 86].

This would open up novel approaches for the treatment and eradication of pathogenic bacteria utilizing inhibitors or modulators of these global loci to vanquish the global concerns of antimicrobial resistance and immune evasion of microbial pathogens. Among these approaches, the interesting inhibitor of SarA (SarABI), 4-[(2,4-diflurobenzyl)amino] cyclohexanol, was confirmed as SarAbased new curative medicament against *S. aureus*-related infections [87]. This might encourage research groups for screening other compounds that might affect global regulators in bacteria to give a new therapy for multi-drug resistant (MDR) bacterial strains.

**197**

tooth models [98].

*2.3.2 Surfactants*

*New Approaches for Competing Microbial Resistance and Virulence*

Biofilm is a sessile community of microbial cells that is found to be attached to animate or inanimate surface, and usually surrounded by a matrix of polysaccharides, proteins and DNA [6]. The cells in these sessile communities differs phenotypically form those present in planktonic communities [88]. Bacterial cells in planktonic forms are almost one thousand times more sensitive to antibiotics than their biofilm counterparts [7]. Additionally, biofilms act as a defense mechanism against different

In this part, we will focus on the agents that are known to exhibit antibiofilm

Antimicrobial peptides (AMPs) that are crucial players of innate immunity are reported to prevent biofilm formation in different pathogens. AMPs with antibiofilm activity are either natural or synthetic. The human cathelicidin peptide, LL-37, has been demonstrated to have antibiofilm activity in case of *P. aeruginosa* (at a concentration of 0.5 μg/mL), while the minimum inhibitory concentration for planktonic cells was 64 μg/mL [90]. In this study, it was reported that LL-37 was able to interfere with the adherence of microbial cells, enhancing twitching motility and downregulation of genes required for biofilm formation via affecting quorum sensing systems (Las and Rhl) [90]. Furthermore, such peptide was shown to prevent biofilm formation in *E. coli* and *S. aureus* [91]. The mouse cathelicidinderived peptide AS10 was reported to exhibit antibiofilm activity in *Candida albicans* [92]. The synthetic cathelicidin-derived peptides; peptide 1018, DJK5 and DJK6, were reported to prevent biofilm formation in addition to enhancement of biofilm dispersion via prompting the hydrolysis of nucleotide signaling systems,

Another synthetic peptide, S4(1–16) M4Ka, has been found to inhibit biofilm formation and detach bacterial cells in *P. aeruginosa* [94]. The human β-defensin 3 (hBD-3) was found to inhibit the expression of *icaA*, *icaD* and *icaR* genes of *Staphylococcus epidermidis,* thus interfering with biofilm formation, where biofilm formation in *Staphylococci* is dependent on the synthesis of the polysaccharide intercellular adhesin PIA encoded by *icaADBC* locus [95]. Another example of human AMP with antibiofilm activity in *S. epidermidis*, is the liver-derived hepcidin 20. This peptide can inhibit extracellular matrix formation of biofilms via targeting PIA [95]. The natural AMP piscidin-3, obtained from fish, exhibits nucleosidase activity and can degrade extracellular DNA of *P. aeruginosa* [96]. Another example of natural AMP, that possesses antibiofilm activity, is esculentin, which is obtained from frog's skin. It acts by permeabilization of the cellular membrane of *P. aeruginosa* PAO1 cells in the biofilm [97]. A synthetic peptide P1, derived from a tick antifreeze protein, significantly inhibited biofilm formation in *Streptococcus mutans*. Such peptide reduced biofilm biomass by about 75% in microtiter plates and *in vitro* 

The anionic surfactant, sodium dodecyl sulfate, has been reported to destruct

biofilm via enhancing the formation of central cavity within biofilm [99]. Cetyltrimethylammonium bromide (Catanionic surfactant), together with application of high shear stress, increased the detachment of *Pseudomonas fluorescens* biofilms [100]. The non-ionic surfactants, polyoxy ethylene sorbitan monolaurate

*DOI: http://dx.doi.org/10.5772/intechopen.90388*

**2.3 Biofilm inhibition and eradication**

stress conditions or immune cells attack [89].

and therefore, leads to its depletion in bacteria [93].

activity.

*2.3.1 Antimicrobial peptides*
