Fatty acid synthesis is a target for antibacterial activity of unsaturated fatty acids

Abstract

Long-chain unsaturated fatty acids, such as linoleic acid, show antibacterial activity and are the key ingredients of antimicrobial food additives and some antibacterial herbs. However, the precise mechanism for this antimicrobial activity remains unclear. We found that linoleic acid inhibited bacterial enoyl-acyl carrier protein reductase (FabI), an essential component of bacterial fatty acid synthesis, which has served as a promising target for antibacterial drugs. Additional unsaturated fatty acids including palmitoleic acid, oleic acid, linolenic acid, and arachidonic acid also exhibited the inhibition of FabI. However, neither the saturated form (stearic acid) nor the methyl ester of linoleic acid inhibited FabI. These FabI-inhibitory activities of various fatty acids and their derivatives very well correlated with the inhibition of fatty acid biosynthesis using [ 14 C] acetate incorporation assay, and importantly, also correlated with antibacterial activity. Furthermore, the supplementation with exogenous fatty acids reversed the antibacterial effect of linoleic acid, which showing that it target fatty acid synthesis. Our data demonstrate for the first time that the antibacterial action of unsaturated fatty acids is mediated by the inhibition of fatty acid synthesis.

Antibacterial targets in fatty acid biosynthesis

“…Screens for FabI (the enoyl ACP reducutase) inhibitors lead to recurrent isolation of unsaturated long chain fatty acids [15]. An examination of their effects on this enzyme and on the viability of several bacteria has revealed they inhibit the S. aureus and E. coli FabI by binding to free enzyme and to its NADH complex.…”

ANTIFUNGAL ACTIVITY OF Cirsium arvense EXTRACTS AGAINST PHYTOPATHOGENIC FUNGUS Macrophomina phaseolina

“…Figure 5 shows the structures of the isolated compounds. The most frequently occurring compound 10-octadecanoic acid, methyl ester is known to have antimicrobial activity (Zheng et al, 2005). Among others, 2H-1-benzopyran, 6,7-dimethoxy-2-2-dimethyl; hexadecanoic acid, methyl ester; 9,12-octadecadienoic acid (Z,Z)-, methyl ester; phytol and 1,2-Benzenedicarboxylic acid, mono (2-ethylhexyl) ester are known to have antifungal and antimicrobial activities, as shown in Table 3.…”

Macrolactin S, a New Antibacterial Agent with Fab G-inhibitory Activity from Bacillus sp. AT28

“…Triclosan and isoniazid, which are currently used antibacterial agents, have been demonstrated to act by inhibiting FabI [5,6]. Cephalochromin and unsaturated fatty acids acting as FabI inhibitors [7,8], atromentin acting as a FabK inhibitor [9], cerulenin and thiolactomycin acting as FabH/B inhibitors [3], and platensimycin and phomallenic acid acting as FabF inhibitors [10,11] were isolated from microorganisms. However, a FabG inhibitor of microbial origin has not been reported.…”