Cationic polymer contributes to broaden the spectrum of vancomycin activity achieving eradication of Pseudomonas aeruginosa

Abstract

Vancomycin (VAN) is unable to penetrate the outer membrane of Gram-negative bacteria and reach the target site. One approach to overcome this limitation is to associate it with compounds with permeabilizing or antimicrobial properties. EudragitE100® (Eu) is a cationic polymer insufficiently characterized for its potential antimicrobial action. Eu-VAN combinations were characterized, the antimicrobial efficacy against Pseudomonas aeruginosa was evaluated and previous studies on the effects of Eu on bacterial envelopes were extended. Time-kill assays showed eradication of P.aeruginosa within 3-6 h exposure to Eu-VAN, whilst VAN was ineffective. Eu showed regrowth in 24 h and delayed colony pigmentation. Although permeabilization of bacterial envelopes or morphological alterations observed by TEM and flow cytometry after exposure to Eu were insufficient to cause bacterial death, they allowed access of VAN to the target site, since Eu-VAN/Van-FL-treated cultures showed fluorescent staining in all bacterial cells, indicating Van-FL internalization. Consequently, Eu potentiated the activity of an otherwise inactive antibiotic against P. aeruginosa. Moreover, Eu-VAN combinations exhibited improved physicochemical properties and could be used in the development of therapeutic alternatives in the treatment of bacterial keratitis.

On-Demand Sequential Release of Dual Drug from pH-Responsive Electrospun Janus Nanofiber Membranes toward Wound Healing and Infection Control

“…It is, therefore, justified to conclude that this was, too, due to the synergy of EE and OCT. In accordance with our results, the bactericidal effect of EE against another Gram-negative Pseudomonas aeruginosa was previously reportedin works by Romero et al and Corti et al , Bacterial membrane damage, i.e., permeabilization of bacterial envelopes and morphological alterations, were observed, but there was none or little cell death in contact with drug-free EE. However, in both cases, the killing effect obtained using the EE drug delivery system was not observed with the drug itself, which was assigned to its cationic nature that contributed to interactions between the incorporated drug and the negatively charged bacterial cell.…”

TMPyP‐mediated photoinactivation of Pseudomonas aeruginosa improved in the presence of a cationic polymer

“…Although a reduction between 1.5 and 3.5 log 10 of the viable count was observed after brief periods of exposure to Eu alone (Figure 1C,D), depending on the polymer concentration and exposure time analyzed, the counts recovered to the level of the untreated control after 24 h, as already reported in previous studies. 35,36 The results indicate that the three combinations Eu + TMPyP exhibited improved photoinactivation against P. aeruginosa (Figure 1C,D), with a significant reduction in the viable count with respect to their components evaluated individually after 30 min of irradiation (p < 0.05). At shorter irradiation time, only the highest concentration of Eu tested in combination with TMPyP exhibited significant differences.…”

“…An accurately weighed quantity of polymer was dissolved in a minimum volume of acetone; and 1.0 N HCl (volume equivalent to 50% of the amino groups of the polymer) was subsequently added to overcome solubility limitations, as previously reported. [35][36][37] After evaporating the solvent, the obtained powder (Eu) was used to prepare aqueous dispersions. Eu + TMPyP combinations were prepared by adding aliquots of stock solution dilutions of TMPyP to aqueous dispersions of Eu.…”

“…In previous studies, we demonstrated that this cationic polymer produces alterations and damage at the level of bacterial envelopes of P. aeruginosa, which led to improved efficacy of fluoroquinolones against resistant strains and a broadening of the spectrum of action of glycopeptides, enabling the inactivation of P. aeruginosa. 35,36 Since P. aeruginosa represents a very difficult target to inactivate, in the present study, we focused our attention on the photoinactivation of this Gram-negative pathogen mediated by TMPyP and addressed aspects so far unreported about the effect of this cationic porphyrin on P. aeruginosa. In addition, we investigated the effect of the cationic polymer Eu in combination with TMPyP on its efficacy in the photoinactivation of this opportunistic pathogen that causes multiple infections that are difficult to treat.…”

Recent Advances in the Development of Lipid-, Metal-, Carbon-, and Polymer-Based Nanomaterials for Antibacterial Applications

“…Manipulation of the sequence of hydrophobic and hydrophilic subunits of antimicrobial polymers is an important factor in achieving facial amphiphilicity for antibacterial activity. A recent study combining vancomycin with the cationic polymer Eudragit E100 ® (Eu) against P. aeruginosa showed that P. aeruginosa was eradicated within 3–6 h of exposure with this combination treatment [ 105 ]. Although bacterial envelope permeabilization and morphological changes after exposure to Eu were not sufficient to cause bacterial death, they allowed vancomycin to enter the target site, thereby enhancing the activity of an otherwise inactive vancomycin against P. aeruginosa .…”