Normal level of sepsis-associated phenylcarboxylic acids in human serum.

Previous studies showed that large amounts of phenylcarboxylic acids (PhCAs) are accumulated in a septic patient's blood due to increased endogenous and microbial phenylalanine and tyrosine biotransformation. Frequently, biochemical aromatic amino acid transformation into PhCAs is considered functionally insignificant for people without monogenetic hereditary diseases. The blood of healthy people contains the same PhCAs that are typical for septic patients as shown in this paper. The overall serum PhCAs level was 6 µM on average as measured by gas chromatography with flame ionization detection. This level is a stable biochemical parameter indicating the normal metabolism of aromatic amino acids. The concentrations of PhCAs in the metabolic profile of healthy people are distributed as follows: phenylacetic ≈ p-hydroxyphenyllactic > p-hydroxyphenylacetic > phenyllactic ≈ phenylpropionic > benzoic. We conclude that maintaining of stable PhCAs level in the serum is provided as the result of integration of human endogenous metabolic pathways and microbiota.

[Influence of Microbial Metabolites of Phenolic Nature on the Activity of Mitochondrial Enzymes].

The aim of this work was to study the effect of microbial metabolites of phenolic nature on the activity of enzymes of the tricarboxylic acid cycle in isolated mitochondria, and determine metabolites of the tricarboxylic acid cycle as potential biomarkers of mitochondrial dysfunction in the blood of patients with sepsis. It is shown that microbial metabolites of phenolic nature have an inhibitory effect on the activity of dehydrogenases, determined by the reduction of dichlorophenolindophenol and nitroblue tetrazolium in liver mitochondria and liver homogenates. This effect is more pronounced in oxidation of the NAD-dependent substrates than succinate oxidation, and at lower concentrations of microbial metabolites than inhibition of respiration. By gas chromatography-mass spectrometry it was found that the content of the tricarboxylic acid cycle metabolites in the blood of patients with sepsis decreased compared to healthy donors. The data obtained show that the microbial phenolic acids can contribute significantly to the dysfunction of mitochondria and suppression of general metabolism, characteristic of these pathologies.

Microbial origin of phenylcarboxylic acids in the human body.

In previous studies we demonstrated increased amounts of phenylcarboxylic acids (PCA) in serum of patients with sepsis. This observation prompted the present study of the ability of the human microbiome bacteria to produce PCA in vitro. PCA were detected in culture media by gas chromatography-mass spectrometry. Increased amounts of phenyllactic and p-hydroxyphenyllactic acids were produced by Klebsiella pneumonia, Escherichia coli, and Staphylococcus aureus. Certain strict anaerobes (bifidobacteria, lactobacteria, eubacteria) have also been found to actively produce these PCA, but these bacteria are not etiologically linked to sepsis. Thus our results demonstrate the ability of sepsis-related bacteria to produce PCA and provide experimental support for the theory that the accumulation of PCA in the blood of patients with sepsis results from microbial degradation of phenylalanine and tyrosine.

Sensitized fluorescence of silver nanoparticles in the presence of pyrene.

The fluorescence of pyrene adsorbed onto the surface of the cetyltrimethylammonium-coated silver nanoparticles was studied. Pyrene molecules adsorbed on freshly prepared silver particles were found to be in close proximity to silver surface thus providing the possibility of energy transfer from excited pyrene to silver cores of the particles. In that case along with the expected fluorescence of pyrene we observed the fluorescence of the silver nanoparticles induced by the excited pyrene molecules. In due course the restructuring of the cetyltrimethylammonium layer resulted in moving of pyrene molecules away from silver surface and simultaneous disappearance of the silver nanoparticles fluorescence band. These data strongly support the recent hypothesis of fluorophore-plasmon coupled emission.

A versatile synthesis of highly bactericidal Myramistin® stabilized silver nanoparticles.

Silver nanoparticles stabilized by a well-known antibacterial surfactant benzyldimethyl[3-(myristoylamino)propyl]ammonium chloride (Myramistin(®)) were produced for the first time by borohydride reduction of silver chloride sol in water. Stable aqueous dispersions of silver nanoparticles without evident precipitation for several months could be obtained. In vitro bactericidal tests showed that Myramistin(®) capped silver NPs exhibited notable activity against six different microorganisms-gram-positive and gram-negative bacteria, yeasts and fungi. The activity was up to 20 times higher (against E. coli) compared to Myramistin(®) at the same concentrations and on average 2 times higher if compared with citrate-stabilized NPs.