Polyamine Catabolism Revisited: Acetylpolyamine Oxidase Plays a Minor Role due to Low Expression.

Biogenic polyamines are ubiquitous compounds. Dysregulation of their metabolism is associated with the development of various pathologies, including cancer, hyperproliferative diseases, and infections. The canonical pathway of polyamine catabolism includes acetylation of spermine and spermidine and subsequent acetylpolyamine oxidase (PAOX)-mediated oxidation of acetylpolyamines (back-conversion) or their direct efflux from the cell. PAOX is considered to catalyze a non-rate-limiting catabolic step. Here, we show that PAOX transcription levels are extremely low in various tumor- and non-tumor cell lines and, in most cases, do not change in response to altered polyamine metabolism. Its enzymatic activity is undetectable in the majority of cell lines except for neuroblastoma and low passage glioblastoma cell lines. Treatment of A549 cells with N1,N11-diethylnorspermine leads to PAOX induction, but its contribution to polyamine catabolism remains moderate. We also describe two alternative enzyme isoforms and show that isoform 4 has diminished oxidase activity and isoform 2 is inactive. PAOX overexpression correlates with the resistance of cancer cells to genotoxic antitumor drugs, indicating that PAOX may be a useful therapeutic target. Finally, PAOX is dispensable for the replication of various viruses. These data suggest that a decrease in polyamine levels is achieved predominantly by the secretion of acetylated spermine and spermidine rather than by back-conversion.

Genetic changes in the FH gene cause vagal paraganglioma.

Vagal paraganglioma (VPGL) is a rare neuroendocrine tumor that originates from the paraganglion associated with the vagus nerve. VPGLs present challenges in terms of diagnostics and treatment. VPGL can occur as a hereditary tumor and, like other head and neck paragangliomas, is most frequently associated with mutations in the SDHx genes. However, data regarding the genetics of VPGL are limited. Herein, we report a rare case of a 41-year-old woman with VPGL carrying a germline variant in the FH gene. Using whole-exome sequencing, a variant, FH p.S249R, was identified; no variants were found in other PPGL susceptibility and candidate genes. Loss of heterozygosity analysis revealed the loss of the wild-type allele of the FH gene in the tumor. The pathogenic effect of the p.S249R variant on FH activity was confirmed by immunohistochemistry for S-(2-succino)cysteine (2SC). Potentially deleterious somatic variants were found in three genes, SLC7A7, ZNF225, and MED23. The latter two encode transcriptional regulators that can impact gene expression deregulation and are involved in tumor development and progression. Moreover, FH-mutated VPGL was characterized by a molecular phenotype different from SDHx-mutated PPGLs. In conclusion, the association of genetic changes in the FH gene with the development of VPGL was demonstrated. The germline variant FH: p.S249R and somatic deletion of the second allele can lead to biallelic gene damage that promotes tumor initiation. These results expand the clinical and mutation spectra of FH-related disorders and improve our understanding of the molecular genetic mechanisms underlying the pathogenesis of VPGL.

Anaerobic methane oxidation is quantitatively important in deeper peat layers of boreal peatlands: Evidence from anaerobic incubations, in situ stable isotopes depth profiles, and microbial communities.

Boreal peatlands store most of their carbon in layers deeper than 0.5 m under anaerobic conditions, where carbon dioxide and methane are produced as terminal products of organic matter degradation. Since the global warming potential of methane is much greater than that of carbon dioxide, the balance between the production rates of these gases is important for future climate predictions. Herein, we aimed to understand whether anaerobic methane oxidation (AMO) could explain the high CO2/CH4 anaerobic production ratios that are widely observed for the deeper peat layers of boreal peatlands. Furthermore, we quantified the metabolic pathways of methanogenesis to examine whether hydrogenotrophic methanogenesis is a dominant methane production pathway for the presumably recalcitrant deeper peat. To assess the CH4 cycling in deeper peat, we combined laboratory anaerobic incubations with a pathway-specific inhibitor, in situ depth patterns of stable isotopes in CH4, and 16S rRNA gene amplicon sequencing for three representative boreal peatlands in Western Siberia. We found up to a 69 % reduction in CH4 production due to AMO, which largely explained the high CO2/CH4 anaerobic production ratios and the in situ depth-related patterns of δ13C and δD in methane. The absence of acetate accumulation after inhibiting acetotrophic methanogenesis and the presence of sulfate- and nitrate-reducing anaerobic acetate oxidizers in the deeper peat indicated that these microorganisms use SO42- and NO3- as electron acceptors. Acetotrophic methanogenesis dominated net CH4 production in the deeper peat, accounting for 81 ± 13 %. Overall, anaerobic oxidation is quantitatively important for the methane cycle in the deeper layers of boreal peatlands, affecting both methane and its main precursor concentrations.

ITS and 16S rDNA metagenomic dataset of different soils from flax fields.

Flax (Linum usitatissimum L.), one of the important and versatile crops, is used for the production of oil and fiber. To obtain high and stable yields of flax products, L. usitatissimum varieties should be cultivated under optimal conditions, including the composition of the soil microbiome. We evaluated the diversity of microorganisms in soils under conditions unfavorable for flax cultivation (suboptimal acidity or herbicide treatment) or infected with causative agents of harmful flax diseases (Septoria linicola, Colletotrichum lini, Melampsora lini, or Fusarium oxysporum f. sp. lini). For this purpose, twenty-two sod-podzolic soil samples were collected from flax fields and their metagenomes were analyzed using the regions of 16S ribosomal RNA gene (16S rDNA) and internal transcribed spacers (ITS) of the ribosomal RNA genes, which are used in phylogenetic studies of bacteria and fungi. Amplicons were sequenced on the Illumina MiSeq platform (reads of 300 + 300 bp). On average, we obtained 8,400 reads for ITS and 43,300 reads for 16S rDNA per sample. For identification of microorganisms in the soil samples, the Illumina reads were processed using DADA2. The raw data are deposited in the Sequence Read Archive under the BioProject accession number PRJNA956957. Tables listing the microorganisms identified in the soil samples are available in this article. The obtained dataset can be used to analyze the fungal and bacterial composition of flax field soils and their relationship to environmental conditions, including suboptimal soil acidity and infection with fungal pathogens. In addition, it can help to understand the influence of herbicide treatment on the microbial diversity of flax fields. Another useful application of our data is the ability to assess the suitability of the soil microbiome for flax cultivation.

Culturable Bacterial Endophytes of Wild White Poplar (Populus alba L.) Roots: A First Insight into Their Plant Growth-Stimulating and Bioaugmentation Potential.

The white poplar (Populus alba L.) has good potential for a green economy and phytoremediation. Bioaugmentation using endophytic bacteria can be considered as a safe strategy to increase poplar productivity and its resistance to toxic urban conditions. The aim of our work was to find the most promising strains of bacterial endophytes to enhance the growth of white poplar in unfavorable environmental conditions. To this end, for the first time, we performed whole-genome sequencing of 14 bacterial strains isolated from the tissues of the roots of white poplar in different geographical locations. We then performed a bioinformatics search to identify genes that may be useful for poplar growth and resistance to environmental pollutants and pathogens. Almost all endophytic bacteria obtained from white poplar roots are new strains of known species belonging to the genera Bacillus, Corynebacterium, Kocuria, Micrococcus, Peribacillus, Pseudomonas, and Staphylococcus. The genomes of the strains contain genes involved in the enhanced metabolism of nitrogen, phosphorus, and metals, the synthesis of valuable secondary metabolites, and the detoxification of heavy metals and organic pollutants. All the strains are able to grow on media without nitrogen sources, which indicates their ability to fix atmospheric nitrogen. It is concluded that the strains belonging to the genus Pseudomonas and bacteria of the species Kocuria rosea have the best poplar growth-stimulating and bioaugmentation potential, and the roots of white poplar are a valuable source for isolation of endophytic bacteria for possible application in ecobiotechnology.