Interactions of Cyclic Hydrocarbons with Biological Membranes

Many cyclic hydrocarbons, e.g. aromatics, cycloalkanes, and terpenes, are toxic to microorganisms. The primary site of the toxic action is probably the cytoplasmic membrane, but the mechanism of the toxicity is still poorly understood. The effects of cyclic hydrocarbons were studied in liposomes prepared from Escherichia coli phospholipids. The membrane-buffer partition coefficients of the cyclic hydrocarbons revealed that these lipophilic compounds preferentially reside in the membrane. The partition coefficients closely correlated with the partition coefficients of these compounds in a standard octanol-water system. The accumulation of hydro carbon molecules resulted in swelling of the membrane bilayer, as assessed by the release of fluorescence self-quenching of fluorescent fatty acid and phospholipid analogs. Parallel to the expansion of the membrane, an increase in membrane fluidity was observed. These effects on the integrity of the membrane caused an increased passive flux of protons and carboxyfluorescein. In cytochrome c oxidase containing proteoliposomes, both components of the proton motive force, the pH gradient and the electrical potential, were dissipated with increasing concentrations of cyclic hydrocarbons. The dissipating effect was primarily the result of an increased permeability of the membrane for protons (ions). At higher concentrations, cytochrome c oxidase was also inactivated. The effective concentrations of the different cyclic hydrocarbons correlated with their partition coefficients between the membrane and aqueous phase. The impairment of microbial activity by the cyclic hydrocarbons most likely results from hydrophobic interaction with the membrane, which affects the functioning of the membrane and membrane-embedded proteins

Effects of the Membrane Action of Tetralin on the Functional and Structural Properties of Artificial and Bacterial Membranes

Tetralin is toxic to bacterial cells at concentrations below 100-mu-mol/liter. To assess the inhibitory action of tetralin on bacterial membranes, a membrane model system, consisting of proteoliposomes in which beef heart cytochrome c oxidase was reconstituted as the proton motive force-generating mechanism, and several gram-positive and gram-negative bacteria were studied. Because of its hydrophobicity, tetralin partitioned into lipid membranes preferentially (lipid/buffer partition coefficient of tetralin is approximately 1,100). The excessive accumulation of tetralin caused expansion of the membrane and impairment of different membrane functions. Studies with proteoliposomes and intact cells indicated that tetralin makes the membrane permeable for ions (protons) and inhibits the respiratory enzymes, which leads to a partial dissipation of the pH gradient and electrical potential. The effect of tetralin on the components of the proton motive force as well as disruption of protein-lipid interaction(s) could lead to impairment of various metabolic functions and to low growth rates. The data offer an explanation for the difficulty in isolating and cultivating microorganisms in media containing tetralin or other lipophilic compounds.</p

Effects of the Membrane Action of Tetralin on the Functional and Structural Properties of Artificial and Bacterial Membranes

Tetralin is toxic to bacterial cells at concentrations below 100-mu-mol/liter. To assess the inhibitory action of tetralin on bacterial membranes, a membrane model system, consisting of proteoliposomes in which beef heart cytochrome c oxidase was reconstituted as the proton motive force-generating mechanism, and several gram-positive and gram-negative bacteria were studied. Because of its hydrophobicity, tetralin partitioned into lipid membranes preferentially (lipid/buffer partition coefficient of tetralin is approximately 1,100). The excessive accumulation of tetralin caused expansion of the membrane and impairment of different membrane functions. Studies with proteoliposomes and intact cells indicated that tetralin makes the membrane permeable for ions (protons) and inhibits the respiratory enzymes, which leads to a partial dissipation of the pH gradient and electrical potential. The effect of tetralin on the components of the proton motive force as well as disruption of protein-lipid interaction(s) could lead to impairment of various metabolic functions and to low growth rates. The data offer an explanation for the difficulty in isolating and cultivating microorganisms in media containing tetralin or other lipophilic compounds

Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

<p>Abstract</p> <p>Background</p> <p>Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia.</p> <p>Methods</p> <p>A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics.</p> <p>Results</p> <p>The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90%) and specificity (85%).</p> <p>Conclusion</p> <p>These findings may have clinical implications for risk-based antimicrobial treatment strategies.</p