Unsaturated Fatty Acids Control Biofilm Formation of Staphylococcus aureus and Other Gram-Positive Bacteria

Abstract

Infections involving biofilms are difficult to treat due to increased resistances against antibiotics and the immune system. Hence, there is an urgent demand for novel drugs against biofilm infections. During our search for novel biofilm inhibitors from fungi, we isolated linoleic acid from the ascomycete Hypoxylon fragiforme which showed biofilm inhibition of several bacteria at sub-MIC concentrations. Many fatty acids possess antimicrobial activities, but their minimum inhibitory concentrations (MIC) are high and reports on biofilm interferences are scarce. We demonstrated that not only linoleic acid but several unsaturated long-chain fatty acids inhibited biofilms at sub-MIC concentrations. The antibiofilm activity exerted by long-chain fatty acids was mainly against Gram-positive bacteria, especially against Staphylococcus aureus. Micrographs of treated S. aureus biofilms revealed a reduction in the extracellular polymeric substances, pointing to a possible mode of action of fatty acids on S. aureus biofilms. The fatty acids had a strong species specificity. Poly-unsaturated fatty acids had higher activities than saturated ones, but no obvious rule could be found for the optimal length and desaturation for maximal activity. As free fatty acids are non-toxic and ubiquitous in food, they may offer a novel tool, especially in combination with antibiotics, for the control of biofilm infections.

Changes in the Rumen Bacteriome Structure and Enzymatic Activities of Goats in Response to Dietary Supplementation with Schizochytrium spp.

“…Another explanation of PUFA toxicity may be related to metabolic imbalances in acyl CoA metabolism [ 62 ]. Remarkably, recent evidence subverts the aforementioned assumptions, indicating that unsaturated fatty acids did not considerably affect bacterial growth of both Gram-negative and -positive strains [ 63 ], whilst unsaturated fatty acids are involved in the prevention of biofilm formation in Gram-positive bacteria, even at the lowest treated level [ 63 ]. Hence, rumen bacteria populations could return to a planktonic lifestyle if the biofilm is dispersed, making them prone to abiotic factors.…”

The Effect of Forage-to-Concentrate Ratio on Schizochytrium spp.-Supplemented Goats: Modifying Rumen Microbiota

“…This ability may alter the degradation rate of starch in the rumen and consequently its digestibility and propionate production [ 53 ]. Considering that recent studies demonstrate that unsaturated fatty acids such as these presented in microalgae biomass could prevent the formation of bacterial biofilm returning them into a planktonic lifestyle [ 12 ], while ciliate protozoa appear to be the major planktonic bacterial predators [ 54 ], it is plausible to assume that the bacteria abundance may be suppressed in the 20HG-fed goats due to protozoa grazing properties.…”

“…Investigating the inhibition of cellulolytic bacteria in presence of PUFA, there is strong evidence involving severe toxicity of PUFA on the cell membrane particularly of Gram-positive bacteria resulting in metabolic imbalances [ 10 , 11 ]. Additionally, recent evidence proposes that PUFA toxicity does not lie in bacteria disruption per se rather in the prevention of the biofilm formation in Gram-positive bacteria [ 12 ]. In contrast, the mechanism underlies the F:C on ruminal bacteriome appears to be more well-studied as lie in changes in pH [ 76 ].…”

“…in goats diet fed with a moderate forage:concentrate (F:C) ratio of 50:50 increased milk docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), conjugated linoleic acid (CLA) content and ω3/ω6 ratio [ 7 ], while simultaneously decreasing the relative abundance of rumen methanogenic microbes [ 8 , 9 ]. Marine origin PUFA which are included in microalgae biomass could exert toxic effects either against specific rumen microbes [ 10 , 11 ], or bacterial biofilms [ 12 ], inhibiting the biohydrogenation process, resulting in a higher proportion of PUFA in milk and meat of ruminants. Further to the disturbance of the rumen biohydrogenation owing to marine PUFAs, their toxicity could also affect both the viability and metabolism of methanogenic microbes [ 13 ].…”

Bacterial Biofilm Inhibition: A Focused Review on Recent Therapeutic Strategies for Combating the Biofilm Mediated Infections

“…A study made by Harvey et al (2019) has revealed the biofilm inhibitory efficacy of antibacterial lipids on the cariogenic organism Streptococcus mutans by Fluorescent Microscopy using Alexa Fluor ® 647 and SYTO ® 9-labeled dextran conjugate. Further, the biofilm development of Gram-positive bacterial pathogens such as S. epidermidis, S. aureus , and S. mutans has been effectively inhibited by some unsaturated fatty acids such as oleic acid, linoleic acid, and palmitoleic acid ( Yuyama et al, 2020 ). The inhibitory efficacy of the two fatty acids includes docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against Fusobacterium nucleatum and Porphyromonas gingivalis biofilms were recently studied by Sun et al (2016) .…”