Antimicrobial Lipids from Plants and Marine Organisms: An Overview of the Current State-of-the-Art and Future Prospects

In the actual post-antibiotic era, novel ways of rethinking antimicrobial research approaches are more urgent than ever. Natural compounds with antimicrobial activity such as fatty acids and monoacylglycerols have been investigated for decades. Additionally, the interest in other lipid classes as antimicrobial agents is rising. This review provides an overview on the research about plant and marine lipids with potential antimicrobial activity, the methods for obtaining and analyzing these compounds, with emphasis on lipidomics, and future perspectives for bioprospection and applications for antimicrobial lipids. Lipid extracts or lipids isolated from higher plants, algae or marine invertebrates are promising molecules to inactivate a wide spectrum of microorganisms. These lipids include a variety of chemical structures. Present and future challenges in the research of antimicrobial lipids from natural origin are related to the investment and optimization of the analytical workflow based on lipidomics tools, complementary to the bioassay-guided fractionation, to identify the active compound(s). Also, further work is needed regarding the study of their mechanism of action, the structure–activity relationship, the synergistic effect with conventional antibiotics, and the eventual development of resistance to lipids, which, as far as is known, is unlikely.

Antimicrobial Activity of Host-Derived Lipids

Host-derived lipids are increasingly recognized as antimicrobial molecules that function in innate immune activities along with antimicrobial peptides. Sphingoid bases and fatty acids found on the skin, in saliva and other body fluids, and on all mucosal surfaces, including oral mucosa, exhibit antimicrobial activity against a variety of Gram positive and Gram negative bacteria, viruses, and fungi, and reduce inflammation in animal models. Multiple studies demonstrate that the antimicrobial activity of lipids is both specific and selective. There are indications that the site of action of antimicrobial fatty acids is the bacterial membrane, while the long-chain bases may inhibit cell wall synthesis as well as interacting with bacterial membranes. Research in this area, although still sporadic, has slowly increased in the last few decades; however, we still have much to learn about antimicrobial lipid mechanisms of activity and their potential use in novel drugs or topical treatments. One important potential benefit for the use of innate antimicrobial lipids (AMLs) as antimicrobial agents is the decreased likelihood side effects with treatment. Multiple studies report that endogenous AML treatments do not induce damage to cells or tissues, often decrease inflammation, and are active against biofilms. The present review summarizes the history of antimicrobial lipids from the skin surface, including both fatty acids and sphingoid bases, in multiple human body systems and summarizes their relative activity against various microorganisms. The range of antibacterial activities of lipids present at the skin surface and in saliva is presented. Some observations relevant to mechanisms of actions are discussed, but are largely still unknown. Multiple recent studies examine the therapeutic and prophylactic uses of AMLs. Although these lipids have been repeatedly demonstrated to act as innate effector molecules, they are not yet widely accepted as such. These compiled data further support fatty acid and sphingoid base inclusion as innate effector molecules.