Fluconazole-Pyridoxine Bis-Triazolium Compounds with Potent Activity against Pathogenic Bacteria and Fungi Including Their Biofilm-Embedded Forms

Two novel quaternary ammonium salts, bis-triazolium derivatives of fluconazole and pyridoxine, were synthesized by reaction of fluconazole with pyridoxine-based synthetic intermediates. The leading compound demonstrated pronounced antimycotic and antibacterial in vitro activity, comparable to or exceeding that of the reference antifungal (fluconazole, terbinafine) and antibacterial/antiseptic (miramistin, benzalkonium chloride) agents. In contrast to many antimicrobials, the leading compound was also active against biofilm-embedded staphylococci and Escherichia coli. While no biofilm structure destruction occurred, all compounds were able to diffuse into the matrix and reduce the number of colony-forming units by three orders of magnitude at 16 × MBC. The leading compound was significantly less toxic than miramistin and benzalkonium chloride and more toxic than the reference antifungal drugs. The obtained results make the described chemotype a promising starting point for the development of new broad-spectrum antimicrobial therapies with powerful effect on fungal and bacterial pathogens including their biofilm-embedded forms

The impact of Grey Heron (Ardea cinerea L.) colony on soil biogeochemistry and vegetation: a natural long-term in situ experiment in a planted pine forest

Increased anthropogenic pressure including intensification of agricultural activities leads to long-term decline of natural biotopes, with planted forests often considered as promising compensatory response, although reduced biodiversity and ecosystem stability represent their common drawbacks. Here we present a complex investigation of the impact of a large Grey Heron (Ardea cinerea L.) colony on soil biogeochemistry and vegetation in a planted Scots pine forest representing a natural in situ experiment on an engineered ecosystem. After settling around 2006, the colony expanded for 15 years, leading to the intensive deposition of nutrients with feces, food remains and feather thereby considerably altering the local soil biogeochemistry. Thus, lower pH levels around 4.5, 10- and 2-fold higher concentrations of phosphorous and nitrogen, as well as 1.2-fold discrepancies in K, Li, Mn, Zn and Co., respectively, compared to the surrounding control forest area could be observed. Unaltered total organic carbon (Corg) suggests repressed vegetation, as also reflected in the vegetation indices obtained by remote sensing. Moreover, reduced soil microbial diversity with considerable alternations in the relative abundance of Proteobacteria, Firmicutes, Acidobacteriota, Actinobacteriota, Verrucomicrobiota, Gemmatimonadota, Chujaibacter, Rhodanobacter, and Bacillus has been detected. The above alterations to the ecosystem also affected climate stress resilience of the trees indicated by their limited recovery from the major 2010 drought stress, in marked contrast to the surrounding forest (p = 3∙10−5). The complex interplay between geographical, geochemical, microbiological and dendrological characteristics, as well as their manifestation in the vegetation indices is explicitly reflected in the Bayesian network model. Using the Bayesian inference approach, we have confirmed the predictability of biodiversity patterns and trees growth dynamics given the concentrations of keynote soil biogeochemical alternations with correlations R > 0.8 between observations and predictions, indicating the capability of risk assessment that could be further employed for an informed forest management

Effect of extracellular levanase SacC from

The formation of polymicrobial biofilms significantly increases the resistance of bacteria in them to a wide range of antibiotics thus making their eradication challenging in infectious medicine. In recent years, the emergence of a large number of antibiotic-resistant strains has contributed to a significant increase in severe cases of infectious diseases. Natural compounds such as alkaloids, terpenes, bacterial peptides and enzymes have great potential in combating polymicrobial diseases, associated with the biofilm formation. At the same time, the enzymatic treatment of biofilms has a number of advantages, since the enzymes are nontoxic, do not cause resistance and can increase the effectiveness of existing antimicrobials. Here we show that recombinant extracellular levanase SacC can promote the destruction of two-species biofilms S. aureus – P. aeruginosa and increase the effectiveness of antibiotics against bacteria in the biofilm up to 16 times

Universal internucleotide statistics in full genomes: a footprint of the DNA structure and packaging?

Uncovering the fundamental laws that govern the complex DNA structural organization remains challenging and is largely based upon reconstructions from the primary nucleotide sequences. Here we investigate the distributions of the internucleotide intervals and their persistence properties in complete genomes of various organisms from Archaea and Bacteria to H. Sapiens aiming to reveal the manifestation of the universal DNA architecture. We find that in all considered organisms the internucleotide interval distributions exhibit the same [Formula: see text]-exponential form. While in prokaryotes a single [Formula: see text]-exponential function makes the best fit, in eukaryotes the PDF contains additionally a second [Formula: see text]-exponential, which in the human genome makes a perfect approximation over nearly 10 decades. We suggest that this functional form is a footprint of the heterogeneous DNA structure, where the first [Formula: see text]-exponential reflects the universal helical pitch that appears both in pro- and eukaryotic DNA, while the second [Formula: see text]-exponential is a specific marker of the large-scale eukaryotic DNA organization

The liquid mineral- and probiotic-containing feed additives for poultry

In this study, we assessed the biocompatibility of five probiotic lactobacilli strains and characterized sapropel, bentonite, and zeolite from the deposits of Tatarstan Republic in terms of their chemical and mineral compositions, cation exchange capacities, sorption activity, and the structure of the ion exchange and sorption complexes. We also constructed a synbiotic preparation with sapropel, bentonite, and zeolite as carrier matrixes for probiotic lactobacilli and determined their viability in the preparation for two weeks. High ion-exchange and sorption properties of sapropel, bentonite, and zeolite and suitable bacterial survival rate during storage are among the main benefits of the developed poultry feed. The obtained data have a great potential for practical use in the construction of multi-strain liquid probiotics, in which probiotic lactobacilli are immobilized on mixtures of various mineral matrix carriers

PDFs of the internucleotide intervals in the DNA from full genomes of ten different organisms at different evolutionary positions from <i>Archaea</i> and <i>Bacteria</i> to <i>H. Sapiens</i>.

<p>The thin dashed line shows an approximation by a single -exponential, while the thick dashed line shows an approximation by a sum of two -exponentials. For comparison, the dotted line shows the corresponding exponential PDF. The inset shows the evolution of the average interval separately for strongly (G:C) and weakly (A:T) bonded nucleotides.</p

Comparison of the internucleotide interval statistics with the DNA walk analysis: (a) DFA fluctuation functions of the internucleotide intervals (full lines) and of the DNA walks (dashdot lines) and (b) the ACFs of the inter-nucleotide intervals (full lines), all provided for the DNA sequences of <i>H. Sapiens</i> (upper curves in each panel) and <i>Bacteria</i> (lower curves in each panel) full genomes.

<p>For the internucleotide interval sequences, the arguments are multiplied by the average interval to provide all results in the same units of base pairs. Vertical dashed lines refer to the approximate boundaries of characteristic scaling regimes for different hierarchical levels of eukaryotic DNA packaging structure (exemplified for <i>H. Sapiens</i>, following <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112534#pone.0112534-Arneodo1" target="_blank">[2]</a>).</p

New Insight into Secreted Ribonuclease Structure: Binase Is a Natural Dimer

<div><p>The biological effects of ribonucleases (RNases), such as the control of the blood vessels growth, the toxicity towards tumour cells and antiviral activity, require a detailed explanation. One of the most intriguing properties of RNases which can contribute to their biological effects is the ability to form dimers, which facilitates efficient RNA hydrolysis and the evasion of ribonuclease inhibitor. Dimeric forms of microbial RNase binase secreted by <i>Bacillus pumilus</i> (former <i>B. intermedius</i>) have only been found in crystals to date. Our study is the first report directly confirming the existence of binase dimers in solution and under natural conditions of enzyme biosynthesis and secretion by bacilli. Using different variants of gel electrophoresis, immunoblotting, size-exclusion chromatography and mass-spectrometry, we revealed that binase is a stable natural dimer with high catalytic activity.</p></div