Antibiofilm Activity of Essential Fatty Acids Against Candida albicans from Vulvovaginal Candidiasis and Bloodstream Infections

Abstract

Purpose The biofilm formation of Candida albicans is an important virulence factor as it can increase tolerance to conventional antifungal drugs and the host immune system. The study aimed to assess the effect of essential fatty acids (EFAs) against biofilm formation and mature biofilms of C. albicans strains, which were isolated from vulvovaginal candidiasis and candidemia. Methods The biofilm formation ability of C. albicans and antifungal activities of fluconazole were determined. Additionally, the effects of six EFAs [α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LOA), γ-linolenic acid (GLA), and arachidonic acid (AA)] against C. albicans under planktonic and biofilm conditions were evaluated. Results 94.1% of C. albicans exhibited biofilm formation capacity, and 98.5% of C. albicans were susceptible to fluconazole. The biofilms of C. albicans were highly resistant to fluconazole with minimum biofilm eradication concentration values ≥ 64 µg/mL. The EFAs attenuated biofilm formation in a dose-dependent manner, and GLA displayed a remarkable inhibitory activity against biofilm formation of C. albicans . In addition, EPA, DHA, and GLA at 0.1 mM could inhibit the biofilm formation of C. albicans without affecting the planktonic growth rate. Notably, EPA and AA at 1 mM had both inhibitory and eradication activities on C. albicans biofilms. Conclusion This is the first study to directly compare different EFAs for their capacity to affect C. albicans biofilm formation as well as biofilm eradication. These results suggest EPA and AA could serve as potential new antifungal agents for the treatment of clinical infections caused by C. albicans biofilms.

Antimicrobial and antibiofilm effects of essential fatty acids against clinically isolated vancomycin-resistant Enterococcus faecium

“…Multidrug resistance and biofilm make the treatment of VRE-fm strain infection even more challenging. Numerous studies indicate that unsaturated fatty acids have the activity of inhibiting or eradicating of biofilms formed by a wide range of bacteria, including even fungi (Kim et al, 2018;Ramanathan et al, 2018;Cui et al, 2019;Wang et al, 2022). These findings are similar to those in the current study.…”

“…In the study, six EFAs are used to test antimicrobial activity against VREfm. In terms of the chemical structure of EFAs (for example, the number of double bonds, the relative position of the double bonds and the carboxyl group) which was shown in our previous work (Wang et al, 2022), it is difficult to find a pattern to explain the different antibacterial activities displayed by them. The antibacterial effect of EFAs may depend mainly on the interaction between EFAs and the cell membrane of VRE-fm strains, so it is not possible to find a pattern solely from the chemical structure of EFAs.…”

“…The antimicrobial activity of EFAs (ALA, EPA, DHA, LOA, GLA, and AA) was evaluated using a microdilution method as previously reported (Wang et al, 2022). Briefly, VRE-fm isolates (1.0-2.0 × 10 8 CFU/mL) inoculated 1:200 into each well of 96-well round bottom microtiter plates with 200 mL of Mueller Hinton II broth containing different concentrations of EFAs.…”

“…With the increasing severity of traditional antibiotic resistance, unsaturated fatty acids have been reconsidered as antimicrobial agents. Recently, numerous studies indicated that unsaturated fatty acids could also inhibit or eradicate biofilms formed by various microbial pathogens (Kim et al, 2018;Ramanathan et al, 2018;Cui et al, 2019;Wang et al, 2022). Consequently, unsaturated fatty acids could represent the next generation of antimicrobial agents to treat and prevent biofilmassociated infections.…”

Anti-bacterial and anti-biofilm activities of arachidonic acid against the cariogenic bacterium Streptococcus mutans

“…AA, which is released by activated macrophages upon stimulation ( Card et al, 1994 ; Gil-de-Gómez et al, 2020 ), is thought to contribute to their anti-bacterial activities ( Desbois and Smith, 2010 ; Das, 2018 ). Also other fatty acids and their metabolites have been documented to exert anti-bacterial as well as anti-fungal activities ( Zheng et al, 2005 ; Ells et al, 2009 ; Desbois and Smith, 2010 ; Huang et al, 2011 ; Das, 2018 ; Casillas-Vargas et al, 2021 ; Wang et al, 2022 ; Maione et al, 2023 ), and they are involved in the natural anti-bacterial defense of the skin to maintain a homeostatic skin microbiota ( Desbois and Smith, 2010 ). The anti-bacterial activities of free fatty acids have been associated with altered membrane fluidity, pore formation, impaired nutrient uptake, generation of free radicals, and formation of lipid peroxides ( Desbois and Smith, 2010 ; Das, 2018 ).…”