Use of lipids to potentiate the antibacterial activity of aminoglycosides

Abstract

Linolenyl alcohol has been shown to inhibit the in vitro growth of several species of gram-positive bacteria. Since the double bonds in linolenyl alcohol could undergo autooxidation, the antimicrobial activities of saturated primary alcohols of similar molecular sizes against Streptococcus mutans BHT were evaluated. Tridecan-l-ol was identified as the most active compound, eliciting a bacteriostatic effect at concentrations at which growth occurred in the presence of other saturated alcohols or linolenyl alcohol. Evidence is also presented that the combined use of tridecan-l-ol and gentamicin sulfate produces a synergistic effect that is bactericidal to S. mutans BHT. A similar bactericidal response was observed when tridecan-l-ol was combined with other aminoglycosides or tested alone against other strains of S. mutans.When used alone, the aminoglycosides are not active in vitro against enterococci (2, 3). However, when an aminoglycoside is combined with penicillin or other cell-wallactive agents, a bactericidal response is achieved (3, 7). The enhancement by penicillin of the effectiveness of aminoglycosides is due to increased intracellular penetration by the aminoglycoside (7). This permeability change could result from the binding of the ,-lactam antibiotic to proteins associated with cell wall synthesis (7, 10) or from a change in the cell wall structure (8).Recently, low concentrations of linolenyl alcohol have been shown to inhibit growth of Streptococcus mutans and other gram-positive bacteria in cultures (4). In this instance, the alcohol was proposed to act as a molecular spacer between the hydrocarbon chains of the acyl-phosphatides, changing the structure of the plasma membrane and increasing its permeability (4).Since the combination of penicillin with an aminoglycoside elicits an enhanced antibacterial response, perhaps a similar potentiation could be obtained upon combination of an aminoglycoside and a long-chain primary alcohol. S. mutans BHT or other strains were used as examples of the streptococcal species. Several primary aliphatic alcohols were compared with linolenyl alcohol to identify the compound with the greatest antibacterial activity. This compound, tridecan-1-ol, was combined with gentamicin and several other aminoglycosides to ascertain whether antibacterial activity could be potentiated.MATERIALS AND METHODS Growth assay. In our laboratory, S. mutans BHT has been studied in detail as an example of the viridans group streptococci. The procedures used to culture this bacterium and to estimate growth from turbidity measurement have been published (4). The effect of the long-chain alcohol, an aminoglycoside, or a combination of these two substances on the growth of S. mutans BHT and other species of streptococci was determined by the following method.Stock solutions of the aminoglycosides were prepared in deionized water and sterilized by filtration through a membrane filter (pore size, 0.22 ,um; Millipore Corp., Bedford, * Corresponding author. t Deceased.Mass.). A sample of the stoc...

7,10-Epoxyoctadeca-7,9-dienoic Acid: A Small Molecule Adjuvant That Potentiates β-Lactam Antibiotics Against Multidrug-Resistant Staphylococcus aureus

“…These two mechanisms might have simultaneously acted to result in strong synergy observed with 7,10-EODA/streptomycin combination. These results are consistent with aminoglycoside potentiating activity of glyceryl monolaurate, tridecan-1-ol against S. aureus strains [22,23]. In our study, chlorpromazine/7,10-EODA combination resulted in synergy against MRSA strains.…”

Hepatoprotective activity of Tridecan-1-ol isolatedfrom Flaveria trinervia (Speng). C. Mohr

“…5E). The bacterio static effect of Tridecan-l-ol was reported by Gilbertson et al, (1984) [24] and Atsushietal., [25]. Tridecan-1-ol has antipest property [ 2 6 ] .…”