Antimicrobial potential of a biosurfactant gel for the prevention of mixed biofilms formed by fluconazole-resistant C. albicans and methicillin-resistant S. aureus in catheters.

Dual-species biofilms formed by Candida albicans and Staphylococcus aureus have high virulence and drug resistance. In this context, biosurfactants produced by Pseudomonas aeruginosa have been widely studied, of which a new derivative (RLmix_Arg) stands out for possible application in formulations. The objective of this study was to evaluate the antibiofilm activity of RLmix_Arg, both alone and incorporated in a gel prepared with Pluronic F-127, against dual-species biofilms of fluconazole-resistant C. albicans (FRCA) and methicillin-resistant S. aureus (MRSA) in impregnated catheters. Broth microdilution tests, MTT reduction assays of mature biofilms, impregnation of RLmix_Arg and its gel in peripheral venous catheters, durability tests and scanning electron microscopy (SEM) were performed. RLmix_Arg showed antimicrobial activity against Candida spp. and S. aureus, by reducing the cell viability of mixed biofilms of FRCA and MRSA, and preventing their formation in a peripheral venous catheter. The incorporation of this biosurfactant in the Pluronic F-127 gel considerably enhanced its antibiofilm activity. Thus, RLmix_Arg has potential application in gels for impregnation in peripheral venous catheters, helping to prevent development of dual-species biofilms of FRCA and MRSA.

Arginine-phenylalanine and arginine-tryptophan-based surfactants as new biocompatible antifungal agents and their synergistic effect with Amphotericin B against fluconazole-resistant Candida strains.

In the past two decades, the increase in microbial resistance to conventional antimicrobials has spurred scientists around the world to search tirelessly for new treatments. Synthetic amino acid-based surfactants constitute a promising alternative to conventional antimicrobial compounds. In this work, two new cationic amino acid-based surfactants were synthesized and their physicochemical, antifungal and antibiofilm properties evaluated. The surfactants were based on phenylalanine-arginine (LPAM) and tryptophan-arginine (LTAM) and prepared from renewable raw materials using a simple chemical procedure. The critical micelle concentrations of the new surfactants were determined by conductivity and fluorescence. Micellization of LPAM and LTAM took place at 1.05 and 0.54 mM, respectively. Both exhibited good antifungal activity against fluconazole-resistant Candida spp. strains, with a low minimum inhibitory concentration (8.2 µg/mL). Their mechanism of action involves alterations in cell membrane permeability and mitochondrial damage, leading to death by apoptosis. Furthermore, when LPAM and LTAM were applied with Amphotericin B, a significant synergistic effect was observed against all the studied Candida strains. These new cationic surfactants are also able to disperse biofilms of Candida spp. at low concentrations. The results indicate that LPAM and LTAM have potential application to combat the advance of fungal resistance as well as microbial biofilms.

Anti-MRSA activity of curcumin in planktonic cells and biofilms and determination of possible action mechanisms.

Staphylococcus aureus is a commensal bacterium and opportunistic human pathogen that can cause a wide variety of clinical infections. It is recognized for its ability to acquire antimicrobial resistance, so methicillin-resistant Staphylococcus aureus (MRSA) infections are a global healthcare challenge. Therefore, the development of new therapeutic options and alternative therapies for treatment is necessary. Curcumin, a polyphenolic substance found in the rhizome of turmeric longa L, has been shown to have several therapeutic properties, including antimicrobial activity. The objective of the study was to evaluate the in vitro antibacterial activity of curcumin alone and associated with oxacillin against MRSA strains, to analyze the mechanism of cell death involved in the isolated action of curcumin by means of flow cytometry and molecular docking, and to verify its superbiofilm action. Curcumin showed antibacterial activity in the range of 125-500 µg/mL against the tested strains, since it caused an increase in membrane permeability and DNA fragmentation, as revealed by flow cytometry analysis. Moreover, it was possible to observe interactions of curcumin with wild-type S. aureus DHFR, S. aureus gyrase and S. aureus gyrase complex with DNA, DNA (5'-D(*CP*GP*AP*TP*GP*CP*G)-3') and Acyl-PBP2a from MRSA by molecular docking. Curcumin also had a synergistic and additive effect when associated with oxacillin, and significantly reduced the cell viability of the analyzed biofilms. Thus, curcumin is a possible candidate for pharmaceutical formulation development for the treatment of MRSA infections.

Rhamnolipids functionalized with basic amino acids: Synthesis, aggregation behavior, antibacterial activity and biodegradation studies.

Rhamnolipids have been intensively studied due to their remarkable properties; however, the biosynthesis of RLs cannot compete commercially with the production of synthetic surfactants. Here, novel cationic rhamnolipids (RLs) derivatives containing arginine and lysine were prepared for the first time using a straightforward synthetic procedure. The RLs used to prepare these new cationic derivatives were produced by Pseudomonas aeruginosa using waste frying oil as carbon source. It was found that the amino acid-based RLs form aggregates at very low concentrations, even below the CMC. Biodegradation studies indicate that these cationic RLs can be classified as readily biodegradable. Interestingly, the RL arginine conjugates exhibited notable DNA binding affinity and good antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, which increases the potential applications of these compounds. Consequently, the use of low-cost substrates and the added value of the final product constitute a more cost-effective rhamnolipid production.