Antimicrobial Activity of Host-Derived Lipids

Abstract

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.

Keywords: antibacterial; antimicrobial lipids; fatty acids; innate immunity; sphingoid bases.

Figure 1

The chemical structures of antimicrobial lipids (AMLs) found on the surface of the skin and oral mucosa. (a) Sapienic acid is the major free fatty acid derived from sebum and lauric acid is the minor fatty acid derivative of sebum. Fatty acids demonstrating antimicrobial activity are generally 12–18 carbons and activity quickly decreases with either longer or shorter chains. Undecylenic acid is derived from sweat and also present on the skin surface. (b) Free sphingoid bases are derived from the stratum corneum, liberated via ceramidases, and exhibit broad antimicrobial activity.