Saturated long chain fatty acids as possible natural alternative antibacterial agents: Opportunities and challenges

The spread of new strains of antibiotic-resistant pathogenic microorganisms has led to the urgent need to discover and develop new antimicrobial systems. The antibacterial effects of fatty acids have been well-known and recognized since the first experiments of Robert Koch in 1881, and they are now used in diverse fields. Fatty acids can prevent the growth and directly kill bacteria by insertion into their membrane. For that, a sufficient amount of fatty acid molecules has to be solubilized in water to transfer from the aqueous phase to the cell membrane. Due to conflicting results in the literature and lack of standardization methods, it is very difficult to draw clear conclusions on the antibacterial effect of fatty acids. Most of the current studies link fatty acids' effectiveness against bacteria to their chemical structure, notably the alkyl chain length and the presence of double bonds in their chain. Furthermore, the solubility of fatty acids and their critical aggregation concentration is not only related to their structure, but also influenced by medium conditions (pH, temperature, ionic strength, etc.). There is a possibility that the antibacterial activity of saturated long chain fatty acids (LCFA) may be underestimated due to the lack of water solubility and the use of unsuitable methods to assess their antibacterial activity. Thus, enhancing the solubility of these long chain saturated fatty acids is the main goal before examining their antibacterial properties. To increase their water solubility and thereby improve their antibacterial efficacy, novel alternatives may be considered, including the use of organic positively charged counter-ions instead of the conventional sodium and potassium soaps, the formation of catanionic systems, the mixture with co-surfactants, and solubilization in emulsion systems. This review summarizes the latest findings on fatty acids as antibacterial agents, with a focus on long chain saturated fatty acids. Additionally, it highlights the different ways to improve their water solubility, which may be a crucial factor in increasing their antibacterial efficacy. We finish with a discussion on the challenges, strategies and opportunities for the formulation of LCFAs as antibacterial agents.