Effect of the Combination of Levofloxacin with Cationic Carbosilane Dendron and Peptide in the Prevention and Treatment of Staphylococcus aureus Biofilms

Abstract

Antibiotic resistance and biofilm-related infections, persistent in conventional antimicrobial treatment, are continuously increasing and represent a major health problem worldwide. Therefore, the development of new effective treatments to prevent and treat biofilm-related infections represents a crucial challenge. Unfortunately, the extensive use of antibiotics has led to an increase of resistant bacteria with the subsequent loss of effectivity of commercial antibiotics, mainly due to antibiotic resistance and the ability of some bacteria to form microbial communities in biotic or abiotic surfaces (biofilms). In some cases, these biofilms are resistant to high concentrations of antibiotics that lead to treatment failure and recurrence of the associated infections. In the fight against microbial resistance, the combination of traditional antibiotics with new compounds (combination therapy) is an alternative that is becoming more extensive in the medical field. In this work, we studied the cooperative effects between levofloxacin, an approved antibiotic, and peptides or cationic dendritic molecules, compounds that are emerging as a feasible solution to overcome the problem of microbial resistance caused by pathogenic biofilms. We studied a new therapeutic approach that involves the use of levofloxacin in combination with a cationic carbosilane dendron, called MalG2(SNHMe2Cl)4, or a synthetic cell-penetrating peptide, called gH625, conjugated to the aforementioned dendron. To carry out the study, we used two combinations (1) levofloxacin/dendron and (2) levofloxacin/dendron-peptide nanoconjugate. The results showed the synergistic effect of the combination therapy to treat Staphylococcus aureus biofilms. In addition, we generated a fluorescein labeled peptide that allowed us to observe the conjugate (dendron-peptide) localization throughout the bacterial biofilm by confocal laser scanning microscopy.

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

“…Scanning electron microscopy (SEM) was performed to evaluate morphological changes in P. aeruginosa cell wall after treatment with dendrimers in TSB at 37 • C for 24 h. The samples for SEM were prepared following the methodology previously described [43,44]. Critical-point drying was carried out with a Polaron CPD7501 critical-point drying system and sputter coated with 200 Å gold-palladium using a Polaron E5400.…”

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.)…”

“…In addition, it has been evaluated against S. aureus biofilms. The results were somewhat worse than against Candida, detecting a MBIC value of 64 mg/L and a MFCB value of 128 mg/L [20]. Some of the dendritic compounds have been synthesized using existing compounds (non-antimicrobials) as molecules to place at focal point positions.…”

Peptides to Overcome the Limitations of Current Anticancer and Antimicrobial Nanotherapies

“…Peptides containing arginines and tryptophans were bound to dendrimers and tested against planktonic persister cells, regular planktonic cells and persister cells in preformed E. coli biofilmst [131,132]. A cationic carbosilane dendrimer functionalized with an antibiotic and a peptide was developed to inhibit the formation of S. aureus biofilms, showing both antibiofilm-damaging and -inhibitory activities [133].…”