The possibility cannot be excluded that the bilayer structure of phospholipids with a hydrophobic alkyl region (interface), which is generated by EPA-containing phospholipids, affects the efflux pumping activity Barasertib clinical trial of compounds including growth inhibitors through the membranes. The hydrophobicity or hydrophilicity of microbial cells varies between microbial species, and these properties are associated with various functions (see Rosenberg & Doyle, 1990). IK-1 cells had a higher hydrophobicity than did IK-1Δ8

cells. No difference in the phospholipid composition was observed between IK-1Δ8 and IK-1 cells (Nishida et al., 2007), suggesting that fatty acid composition (i.e. the presence of EPA) leads to higher hydrophobicity of IK-1 cells. Phospholipid bilayers with a hydrophobic interfacial region are permeable to hydrophobic molecules, and the permeability is greater for more hydrophobic solutes (Cohen & Bangham, 1972). This would be applicable primarily to the outer membrane of Gram-negative bacteria, where the lipid bilayer is formed, because the outer leaflet comprises mainly lipopolysaccharide and the inner leaflet comprises mainly phospholipids (Nikaido & Vaara, 1985), and to the cell membrane (inner membrane), where the outer and inner leaflets comprise phospholipids. The membrane-shielding effect of EPA-containing

phospholipids would operate in both the outer and the inner cell membranes. The lower Nutlin-3 cost MICs of CCCP and DCCD (Table 1) for IK-1 demonstrate that these hydrophobic compounds tend to remain and to operate in Temsirolimus mw the more hydrophobic cell membrane. These data indicate that the fatty acid composition of the outer and inner membranes should

be analysed separately. According to Allen et al. (1999), a deep-sea EPA-producing bacterium, Photobacterium profundum SS9, includes almost similar levels of EPA (∼5% of total fatty acids) in the outer and inner membranes. Interestingly, enhanced EPA producing mutants of the eukaryotic monocellular alga eustigmatophyte, Nannochloropsis oculata, become more resistant to higher concentrations of cerulenin and erythromycin, both of which are slightly water soluble, compared with the wild type (Chaturvedi & Fujita, 2006). For example, the growth of wild-type cells was inhibited completely by cerulenin at a concentration of 25 μM, but cerulenin, at 75 μM, had no effect on the growth of the mutant (CER1). Although the involvement of the membrane-shielding effect of EPA has not been investigated, it may be operative even in eukaryotic organisms. The wild type of this alga contains 16 : 0 (17% of total), 16 : 1 (17%), and EPA (38%) as the major fatty acids, and the contents of EPA and 16 : 0 and 16 : 1 fatty acids increase in antibiotic-resistant mutants. The authors thank Dr Y.