Role of Alcohols in Growth, Lipid Composition, and Membrane Fluidity of Yeasts, Bacteria, and Archaea

Abstract

Increased membrane fluidity, which causes cofactor leakage and loss of membrane potential, has long been documented as a cause for decreased cell growth during exposure to ethanol, butanol, and other alcohols. Reinforcement of the membrane with more complex lipid components is thus thought to be beneficial for the generation of more tolerant organisms. In this study, organisms with more complex membranes, namely, archaea, did not maintain high growth rates upon exposure to alcohols, indicating that more complex lipids do not necessarily fortify the membrane against the fluidizing effects of alcohols. In the presence of alcohols, shifts in lipid composition to more saturated and unbranched lipids were observed in most of the organisms tested, including archaea, yeasts, and bacteria. However, these shifts did not always result in a decrease in membrane fluidity or in greater tolerance of the organism to alcohol exposure. In general, organisms tolerating the highest concentrations of alcohols maintained membrane fluidity after alcohol exposure, whereas organisms that increased membrane rigidity were less tolerant. Altered lipid composition was a common response to alcohol exposure, with the most tolerant organisms maintaining a modestly fluid membrane. Our results demonstrate that increased membrane fluidity is not the sole cause of growth inhibition and that alcohols may also denature proteins within the membrane and cytosol, adversely affecting metabolism and decreasing cell growth.

Effects of low-molecular weight alcohols on bacterial viability

“…As the Gram-negative microorganisms present a thick outer layer of lipopolysaccharide and the inner phospholipidic membrane, it is expected that the alcohols affect this bacterial class efficiently and quickly (15,16). Interestingly, the alcohols inhibited the growth of K. pneumoniae, a bacterium that is part of the same family as E. coli, in a concentration of about 3% V/V, but the bactericidal effect appeared at higher concentrations.…”

Using Transcriptomics To Improve Butanol Tolerance of Synechocystis sp. Strain PCC 6803

“…Solvents compromise the cell membrane and alter membrane fluidity (14). A compromised cell membrane can leak metabolites, resulting in loss of the transmembrane electrochemical gradient and hence of the proton-motive force.…”

Near-Real-Time Analysis of the Phenotypic Responses of Escherichia coli to 1-Butanol Exposure Using Raman Spectroscopy

“…Both short-chain (ϽC 4 ) and long-chain (ϾC 4 ) alcohols are known to cause membrane disruption by mechanisms of desiccation (short-chain alcohols) or intercalation (long-chain alcohols) of lipophilic side chains into the membrane lipid bilayer (15,16,22). In general, increased membrane fluidity has been observed as a result of 1-butanol exposure for both E. coli and a natural 1-butanol producer, Clostridium acetobutylicum (23)(24)(25)(26). This fluidizing effect has been proposed to result from several host response mechanisms, including the following: (i) an altered ratio of saturated versus unsaturated fatty acids in the cell membrane (27), (ii) denatured protein structure and changed cell surface protein composition (26,28), (iii) increased use of efflux pumps in several Gram-negative bacteria (17), (iv) disrupted protein-lipid interactions (25), (v) upregulated synthesis of other protective metabolites and macromolecules (26,28), and (vi) decreased central carbon metabolic activity by inhibition of glucose and nutrient transport (16,21,26,28,29).…”

“…This fluidizing effect has been proposed to result from several host response mechanisms, including the following: (i) an altered ratio of saturated versus unsaturated fatty acids in the cell membrane (27), (ii) denatured protein structure and changed cell surface protein composition (26,28), (iii) increased use of efflux pumps in several Gram-negative bacteria (17), (iv) disrupted protein-lipid interactions (25), (v) upregulated synthesis of other protective metabolites and macromolecules (26,28), and (vi) decreased central carbon metabolic activity by inhibition of glucose and nutrient transport (16,21,26,28,29). The general consensus is that long-chain alcohols have the ability to intercalate further into the membrane lipid bilayer and disrupt hydrogen bonding between hydrophobic tails, causing relatively more toxicity than short-chain alcohols (15,23,27,30). However, this proposed mechanism does not always hold true for 1-butanol, for which toxicity appears to be strain dependent (31).…”

“…The effect of alcohol on microbial cell membrane fluidity has also been studied widely (23,30,32,33). It has been observed that E. coli responds to ethanol exposure with an initial alteration of fatty acid composition as a short-term response, allowing for de novo biosynthesis of membrane components as a permanent and longterm response (23,27,34,35). A net increase in total protein from cells exposed to growth-inhibitory levels of ethanol has also been observed (34).…”