The Antibacterial Effect of PEGylated Carbosilane Dendrimers on P. aeruginosa Alone and in Combination with Phage-Derived Endolysin

Abstract

The search for new microbicide compounds is of an urgent need, especially against difficult-to-eradicate biofilm-forming bacteria. One attractive option is the application of cationic multivalent dendrimers as antibacterials and also as carriers of active molecules. These compounds require an adequate hydrophilic/hydrophobic structural balance to maximize the effect. Herein, we evaluated the antimicrobial activity of cationic carbosilane (CBS) dendrimers unmodified or modified with polyethylene glycol (PEG) units, against planktonic and biofilm-forming P. aeruginosa culture. Our study revealed that the presence of PEG destabilized the hydrophilic/hydrophobic balance but reduced the antibacterial activity measured by microbiological cultivation methods, laser interferometry and fluorescence microscopy. On the other hand, the activity can be improved by the combination of the CBS dendrimers with endolysin, a bacteriophage-encoded peptidoglycan hydrolase. This enzyme applied in the absence of the cationic CBS dendrimers is ineffective against Gram-negative bacteria because of the protective outer membrane shield. However, the endolysin—CBS dendrimer mixture enables the penetration through the membrane and then deterioration of the peptidoglycan layer, providing a synergic antimicrobial effect.

Novel Treatment Approach against Candida spp.: Evaluation of Antifungal and Antibiofilm In Vitro Activity of Dendritic Molecules

“…Therefore, we would be missing tremendously relevant information and we would be giving inaccurate information. However, studies carried out with the resazurin method have shown good efficacy and reliable and complete results [19][20][21][22]. Resazurin does not require additives or dissolve salts with DMSO, as is the case with the dyes mentioned above (Figure 1).…”

“…The use of these dendritic systems has been studied in both gram-negative and gram-positive bacteria [28][29][30][31], including planktonic phase and biofilms [20,22,32,33]. Its efficacy has also been evaluated in eukaryotes, such as yeasts (Candida spp.)…”

“…Despite this, it is possible to find references for effective compounds against microorganisms, especially eukaryotes, with a cytotoxic effect below the MIC and/or MBIC values. Furthermore, adding PEG ligands to dendritic systems structures may solve or improve the cytotoxicity problem as these ligands have been shown to improve biocompatibility as well as solubility [22,44,46]. Another alternative to reduce cytotoxicity is by using synergistic combinations of different compounds.…”

Prevention and Eradication of Biofilm by Dendrimers: A Possibility Still Little Explored

“…Among these combinations, gH625-M/FC and gH625-M/5-FLC proved to be effective against BF, unlike single use, even at high concentrations, of antifungals [ 177 ]. Very recently, the group of Quintana-Sanchez searched for new microbicide compounds against difficult-to-eradicate BF-forming bacteria, studying cationic multivalent dendrimers both as antibacterial agents and as carriers of active molecules [ 178 ]. Particularly, they estimated the antimicrobial activity of cationic CBS dendrimers, unmodified or modified with PEG residues, against planktonic and BF-forming P. aeruginosa colonies.…”

“…This study revealed that the presence of PEG subverted the hydrophilic/hydrophobic balance, and reduced the antibacterial activity, as confirmed by different analytical techniques. On the other hand, the activity was improved by the combination of the CBS dendrimers with endolysin, a bacteriophage-encoded peptidoglycan hydrolase [ 178 ]. This enzyme, when used in the absence of the cationic CBS dendrimers, is ineffective against Gram-negative bacteria due to the protective outer membrane shield.…”