Single- and Double-Chain Arginine-Derived Surfactants: Antimicrobial, Antibiofilm and Synergistic Activities

The rise in antimicrobial resistance and the resilience of microbial biofilms demand innovative strategies that combine, for instance, membrane-active agents with marketed drugs. Arginine-based surfactants are promising alternatives to conventional quaternary ammonium compounds, but comparative data on their antimicrobial, antibiofilm and modulatory activities remain limited. Five arginine-derived surfactants, the single-chain Nα-lauroyl-L-arginine methyl ester (LAM) and ethyl ester (LAE), together with their double-chain homologues LANHC3, LANHC5 and LANHC8 were evaluated against Gram-positive and Gram-negative bacteria and four Candida spp. Minimum inhibitory (MIC) and lethal (MLC) concentrations were determined by broth microdilution method. Antibiofilm activity was assessed through minimum biofilm inhibitory (MBIC) and eradication (MBEC) concentrations. Checkerboard assays were used to evaluate the synergism between the surfactants and conventional therapeutic antibacterial and antifungal agents. LANHC3 and LANHC8 exhibited uniform antibacterial MICs of 19.53 µg/mL, while LAM and LANHC5 showed MICs of 19.53 µg/mL for most strains, with Enterococcus faecalis requiring 39.06 µg/mL. LANHC3 was the most potent surfactant over Candida spp. With MICs of 9.76 µg/mL for all species, and similarly to LAM, both were fungicidal at 39.06 µg/mL. LAM and LANHC3 also showed the lowest MBIC and MBEC values, inhibiting the Candida biofilm formation at 39.06 µg/mL and eradicating mature biofilms at 78.12 µg/mL, while the other surfactants required higher concentrations to disrupt the microbial biofilms. Synergic or additive interactions were found between the surfactants and selected β-lactam and macrolide antibiotics, as well as azole antifungals, with no antagonism observed. LAM and particularly LANHC3 combined broad-spectrum antimicrobial activity, relevant antibiofilm effects and the ability to potentiate the activity of conventional agents, supporting their choice as alternative or complementary antimicrobial adjuvants over resistant microorganisms and their biofilms.