Antifungal and antiprotozoal green amino acid-based rhamnolipids: Mode of action, antibiofilm efficiency and selective activity against resistant Candida spp. strains and Acanthamoeba castellanii

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2020-09, Vol.193, p.111148, Article 111148
• Main Authors: da Silva, Anderson, Nobre, Hélio, Sampaio, Leticia, Nascimento, Bruna do, da Silva, Cecilia, de Andrade Neto, João Batista, Manresa, Ángeles, Pinazo, Aurora, Cavalcanti, Bruno, de Moraes, Manoel Odorico, Ruiz-Trillo, Iñaki, Antó, Meritxell, Morán, Carmen, Pérez, Lourdes
• Format: Article
• Language: English
• Subjects: Acanthamoeba castellanii; Acanthamoeba castellanii - drug effects; Amino acid-based rhamnolipids; Amino Acids - chemistry; Amino Acids - pharmacology; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antifungal and antiprotozoal activities; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Biofilm; Biofilms - drug effects; Candida - drug effects; Candida spp; Drug Resistance, Fungal - drug effects; Glycolipids - chemistry; Glycolipids - pharmacology; Microbial selectivity; Microbial Sensitivity Tests; Molecular Conformation; Parasitic Sensitivity Tests
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2020.111148

[Display omitted] •Cationic rhamnolipids show antifungal activity against Candida resistant strains.•Cationic rhamnolipids can effectively disperse mature biofilms at low concentrations.•Anionic and cationic RLs exhibit antiprotozoal activity against A. castellanii.•The RLs cytotoxicity is lower than their activity against yeast and amoeba strains. Nowadays, infections caused by fungi and protists constitute a serious problem for public health services. The limited number of treatment options coupled with the increasing number of resistant microorganisms makes necessary the development of new non-toxic antifungal and antiprotozoal agents. Cationic amino acid-based rhamnolipids have been recently prepared by our group and exhibited good antibacterial activity. In this work, the antifungal, antibiofilm and antiprotozoal activity of these new rhamnolipids was investigated against a collection of fluconazole-resistant strains of different Candida species and Acanthamoeba castellanii, respectively. The arginine-RLs exhibited good antifungal activity against all fluconazole-resistant Candida spp. strains tested at MICs ranging from 6.5 to 20.7 mg/L. Their mechanism of action involves alterations in the permeability of the cell membranes that provoke death by apoptosis. The Arginine based-RLs also disperse Candida biofilms at low concentrations, similar to the MICs. All RLs tested (anionic and cationic) showed antiprotozoal activity, the arginine derivatives had the best activity killing the Acanthamoeba castellanii at concentrations of 4 mg/L. Interestingly, these surfactants have a wide range of action against yeast and A. castellanii in which they do not show toxicity against keratinocytes and fibroblasts. These results indicate that these new rhamnolipids have a sufficiently wide safety margin to be considered good candidates for several pharmaceutical applications such as combating fungal resistance and microbial biofilms and the formulation of antiprotozoal drugs.