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Subclass IId bacteriocins targeting mannose phosphotransferase system—Structural diversity and implications for receptor interaction and antimicrobial activity
Get PDFThe bacterial mannose phosphotransferase system (Man-PTS) mediates uptake of selected monosaccharides. Simultaneously, it is a receptor for diverse bacteriocins such as subclass IIa pediocin-like bacteriocins and some subclass IId ones (garvicins ABCQ, lactococcins ABZ, BacSJ, ubericin K, and angicin). So far, no attempt has been made to categorize this ever-expanding group of bacteriocins. Here, we identified Man-PTS as a receptor for a number of previously uncharacterized bacteriocins, and demonstrated that they all belong to a large family of Man-PTS-binding nonpediocin-like peptides, providing new insights into their structure and function. Based on amino acid sequence similarities between members of this family, we propose their classification into five groups. This classification conveniently distinguishes bacteriocins with specific structures and properties regarding their spectrum of antimicrobial activity and pattern of interaction with Man-PTS. With respect to the latter, we indicate individual amino acid residues or regions of Man-PTS and the bacteriocin responsible for their interaction. In Man-PTS, these residues localize to the exterior of the transport complex, specifically the extracellular loop of the so-called Vmotif domain-containing regions γ and/or γ+, and to the interior of the transport complex, specifically the interface between the Core and Vmotif domains. Finally, we propose that while the bacteriocins from separate groups display specific binding patterns to Man-PTS, the general mechanism of their interaction with the receptor is universal despite significant differences in their predicted structures, i.e. after initial docking on the bacterial cell through an interaction with the Man-PTS regions γ and/or γ+, they pull away its Core and Vmotif from one another to form a pore across the membrane
Ageing-dependent thiol oxidation reveals early oxidation of proteins with core proteostasis functions
Get PDFOxidative post-translational modifications of protein thiols are well recognized as a readily occurring alteration of proteins, which can modify their function and thus control cellular processes. The development of techniques enabling the site-specific assessment of protein thiol oxidation on a proteome-wide scale significantly expanded the number of known oxidation-sensitive protein thiols. However, lacking behind are large-scale data on the redox state of proteins during ageing, a physiological process accompanied by increased levels of endogenous oxidants. Here, we present the landscape of protein thiol oxidation in chronologically aged wild-type Saccharomyces cerevisiae in a time-dependent manner. Our data determine early-oxidation targets in key biological processes governing the de novo production of proteins, protein folding, and degradation, and indicate a hierarchy of cellular responses affected by a reversible redox modification. Comparison with existing datasets in yeast, nematode, fruit fly, and mouse reveals the evolutionary conservation of these oxidation targets. To facilitate accessibility, we integrated the cross-species comparison into the newly developed OxiAge Database
Daphnia stress response to environmental concentrations of chloramphenicol—multi-omics approach
Get PDFCommonly used medicines, when discarded or improperly disposed of, are known to contaminate freshwater ecosystems. Pharmaceuticals can be toxic and mutagenic, and can modify freshwater organisms, even at environmentally relevant concentrations. Chloramphenicol (CAP) is an antibiotic banned in Europe. However, it is still found in surface waters around the world. The aim of this study was to evaluate the impact of chloramphenicol contamination in freshwater on the model organism Daphnia magna. Specific life history parameters, proteome, and host-associated microbiome of four D. magna clones were analyzed during a three-generation exposure to CAP at environmental concentrations (32 ng L−1). In the first generation, no statistically significant CAP effect at the individual level was detected. After three generations, exposed animals were smaller at first reproduction and on average produced fewer offspring. The differences in D. magna’s life history after CAP treatment were in accordance with proteome changes. D. magna’s response to CAP presence indicates the high stress that the tested organisms are under, e.g., male production, upregulation of ubiquitin-conjugating enzyme E2 and calcium-binding protein, and downregulation of glutathione transferase. The CAP-exposed D. magna proteome profile confirms that CAP, being reactive oxygen species (ROS)-inducing compounds, contributes to structural changes in mitochondria. Microbiome analysis showed a significant difference in the Shannon index between control and CAP-exposed animals, the latter having a more diverse microbiome. Multilevel analyses, together with long exposure in the laboratory imitating conditions in a polluted environment, allow us to obtain a more complete picture of the impact of CAP on D. magna
The role of gut microbiota metabolites in the regeneration and protection of nervous tissue: a narrative review
Get PDFThe gut microbiota modulates various physiological functions in the human body, including digestion, immune regulation, gut barrier maintenance, and even nervous system activity. The bidirectional communication between gut microbes and the brain, known as the microbiota–gut–brain axis, is crucial for balanced metabolism. Recent studies have indicated that gut microbiota metabolites, such as short-chain fatty acids, indole derivatives, neurotransmitters, and other bioactive compounds, can positively impact neurogenesis, myelination, and axonal regeneration, suggesting their potential in therapeutic strategies for neuroprotection and neuroregeneration. Despite the growing number of studies on gut microbiota metabolites, understanding their role in neuroprotective mechanisms remains limited. This article reviews the classification, production, functions and therapeutic potential of the most well-known gut microbiota metabolites, as well as their impact on neurogenesis, synaptogenesis, energy metabolism, immune modulation, and blood–brain barrier integrity, which will provide a foundation for the study of gut microbiota metabolites in the field of biomedical engineering
LCRAnnotationsDB: a database of low complexity regions functional and structural annotations
No full textLow Complexity Regions (LCRs) are segments of proteins with a low diversity of amino acid composition. These regions play important roles in proteins. However, annotations describing these functions are dispersed across databases and scientific literature. LCRAnnotationsDB aims to consolidate knowledge about LCRs and store relevant annotations in a single place. To unify redundant annotations, we assigned them categories based on similarity in function, protein structure, and biological process. Categories are organized hierarchically by linking them to Gene Ontology terms. The LCRAnnotationsDB database can be accessed at https://lcrannotdb.lcr-lab.org/
Cryoprotectant-specific alterations in the proteome of Siberian sturgeon spermatozoa induced by cryopreservation
Get PDFCryopreservation is crucial for conserving genetic diversity in endangered species including the critically endangered group of sturgeons (Acipenseridae), but it can compromise sperm quality and protein profiles. Although cryopreservation with dimethyl sulfoxide (DMSO) and methanol (MeOH) results in the recovery of good post-thaw motility, DMSO-preserved sperm show reduced fertilization ability. This study was conducted in Siberian sturgeon as a model for Acipenserid fishes to explore the effects of DMSO and MeOH on the proteome of semen using advanced proteomics methods—liquid chromatography‒mass spectrometry and two-dimensional difference gel electrophoresis. We analyzed the proteomic profiles of fresh and cryopreserved spermatozoa and their extracellular medium and showed that cryopreservation decreases motility and viability and increases reactive oxygen species levels, membrane fluidity, and acrosome damage. Despite having similar post-thaw semen motility, sperm treated with DMSO had significantly lower fertilization success (6.2%) than those treated with MeOH (51.2%). A total of 224 and 118 differentially abundant proteins were identified in spermatozoa preserved with MeOH and DMSO, respectively. MeOH-related proteins were linked to chromosomal structure and mitochondrial functionality, while DMSO-related proteins impacted fertilization by altering the acrosome reaction and binding of sperm to the zona pellucida and nuclear organization. Additionally, cryopreservation led to alterations in the proacrosin/acrosin system in both cryoprotectants. This study provides the first comprehensive proteomic characterization of Siberian sturgeon sperm after cryopreservation, offering insights into how cryoprotectants impact fertilization ability
Restricting the level of the proteins essential for the regulation of the initiation step of replication extends the chronological lifespan and reproductive potential in budding yeast
Get PDFAging is defined as a progressive decline in physiological integrity, leading to impaired biological function, including fertility, and rising vulnerability to death. Disorders of DNA replication often lead to replication stress and are identified as factors influencing the aging rate. In this study, we aimed to reveal how the cells that lost strict control of the formation of crucial for replication initiation a pre-initiation complex impact the cells' physiology and aging. As strains with the lower pre-IC control (lowPICC) we used, Saccharomyces cerevisiae heterozygous strains having only one functional copy of genes, encoding essential replication proteins such as Cdc6, Dbf4, Sld3, Sld7, Sld2, and Mcm10. The lowPICC strains exhibited a significant reduction in the respective genes' mRNA levels, causing cell cycle aberrations and doubling time extensions. Additionally, the reduced expression of the lowPICC genes led to an aberrant DNA damage response, affected cellular and mitochondrial DNA content, extended the lifespan of post-mitotic cells, and increased the yeast's reproductive potential. Importantly, we also demonstrated a strong negative correlation between the content of cellular macromolecules (RNA, proteins, lipids, polysaccharides) and aging. The data presented here will likely contribute to the future development of therapies for treating various human diseases
Molecular Differences in Mitochondrial Genomes (Mitogenomes) of Dogs with Recurrent and Multiple Tumours and Their Reference to the Human Mitochondrial Genome
Get PDFThe aim of this study was to identify molecular defects caused by mutations in mitochondrial DNA in cases of recurrent and multiple canine tumours. We presented molecular differences in the mtDNA genome for two tumours observed in different body parts of five dogs and throughout time in the case of the recurrence. Mitochondrial DNA was sequenced on an Illumina MiSeq sequencer using a 600-cycle kit in a paired-end mode targeting at least 100x coverage. The sequences obtained were subjected to bioinformatic analyses in order to determine mutation and polymorphic sites within the analysed mtdna genome in the tumour tissue. The total amount of changes: single nucleotide polymorphisms (SNPs), indels, mutations, and heteroplasmy detected in this study was 329. Ten polymorphisms were found in all analysed samples: ins.2679_2680g (tRNA-Leu (UUR)), m.5367c>t (COX1), m.5444t>C (COX1), m.6065a>G (COX1), m.8368c>T (ATP6), m.8807g>A (COX3), ins.9913_9914tg (ND4L), m.13299t>A (ND5), m.15814c>T, and m.16418A>G (control region). Interestingly, the highest number of differences in the mtdna genome was observed between non-cancerous pyogranuloma tissue and epithelioma glandulae sebacei. The mutations in the non-cancerous tissue were mainly found in positions where polymorphisms were observed in blood and tumour tissue. The lowest number of changes was observed for the youngest analysed dog, which may indicate that some changes appeared in the mitogenomes with age. There were fewer heteroplasmic alterations in the larger than smaller tumour, which may suggest that the tumour growth is enhanced by genomic instability. The changes in the protein-coding genes were mostly synonymous, and nonsynonymous changes did not lead to alterations in protein properties. New mutations were observed in the post-recurrence tumours in comparison with the pre-recurrent tissue and blood
Synthesis, Crystal Structure and Supramolecular Features of Novel 2,4-Diaminopyrimidine Salts
Get PDFThe crystal structures and the supramolecular architectures of a series of novel salts originating from 2,4-diaminopyrimidine and four different chain dicarboxylic acids are reported. For this purpose, 2,4-diaminopyrimidin-1-ium 2,2′-thio(acetic)acetate (1), 2,4-diaminopyrimidin-1-ium monoglutarate (2), 2,4-diaminopyrimidin-1-ium 3,3′-dithio(propionic)propionate (3) and 2,4-diaminopyrimidin-1-ium suberate (4) were synthesized in good to high yields from 2,4-diaminopyrimidine and appropriate dicarboxylic acids (2,2′-thiodiacetic acid, glutaric acid, 3,3′-dithiodipropionic acid and suberic acid, respectively). Each of the compounds were formed as a monohydrate and compound 4 additionally co-crystallized with the suberic acid molecule. Despite the similar structures of compounds 1 and 2 as well as 3 and 4, subtle but important differences are observed in their crystal packing and H-bonding patterns, especially between 3 and 4. Supramolecular self-assemblies can be distinguished through different interactions considering anions, leading to diverse H-bonding motifs, which also include sulphur atoms in 1 and 3, at the upper level of supramolecular architecture. Notably, the basic motif is always the same—2,4-diaminopyrimidine-based homosynthon R22(8) via N-H∙∙∙N interactions. The impact of diverse types of intermolecular interactions was evaluated by Hirshfeld analysis, while the propensity of atom pairs of elements to build interactions was calculated using enrichment ratios. Although compounds 1 and 3 contain S-atoms, the percentage of S-derived interactions is rather low. In 1, the contribution of S∙∙∙H/H∙∙∙S, S∙∙∙C/C∙∙∙S, S∙∙∙N/N∙∙∙S intermolecular contacts is 5.7%. In 2, the contribution of S∙∙∙H/H∙∙∙S accounts for only 0.6%
Loss-of-function mutations are main drivers of adaptations during short-term evolution
Get PDFWe noticed that during short-term experimental evolution and carcinogenesis, mutations causing gene inactivation (i.e., nonsense mutations or frameshifts) are frequent. Our meta-analysis of 65 experiments using modified dN/dS statistics indicated that nonsense mutations are adaptive in different experimental conditions and we empirically confirmed this prediction. Using yeast S. cerevisiae as a model we show that fixed or highly frequent gene loss-of-function mutations are almost exclusively adaptive in the majority of experiments