multifunctionality
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INTRODUCTION: One route of translating the information encoded in the glycan chains of cellular glycoconjugates into physiological effects is via receptor (lectin) binding. A family of endogenous lectins, sharing folding, a distinct sequence signature and affinity for β-galactosides (thus termed galectins), does so effectively in a context-dependent manner. AREAS COVERED: An overview is given on the multifunctional nature of galectins, with emphasis on galectin-1. The broad range of functions includes vital processes such as adhesion via glycan bridging, glycoconjugate transport or triggering signaling relevant, for example, for growth regulation. Besides distinct glycoconjugates, this lectin can also interact with certain proteins so that it can target counterreceptors at all sites of location, that is, in the cytoplasm and/or nucleus, at both sides of the membrane or extracellularly. Approaches to strategically exploit galectin activities with therapeutic intentions are outlined. EXPERT OPINION: The wide versatility of sugar coding and the multifunctionality of galectin-1 explain why considering to turn the protein into a therapeutic target is an ambitious aim. Natural pathways shaped by physiologic master regulators (e.g., the tumor suppressor p16(INK4a)) are suggested to teach inspiring lessons as to how the lectin might be recruited to clinical service.
- MeSH
- biologický transport účinky léků MeSH
- buněčná adheze účinky léků MeSH
- cílená molekulární terapie MeSH
- galektin 1 antagonisté a inhibitory metabolismus MeSH
- galektiny antagonisté a inhibitory metabolismus MeSH
- glykokonjugáty metabolismus MeSH
- lidé MeSH
- nádorové proteiny antagonisté a inhibitory metabolismus MeSH
- nádory farmakoterapie prevence a kontrola MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky farmakologie terapeutické užití MeSH
- racionální návrh léčiv * MeSH
- signální transdukce účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Despite their importance, how plant communities and soil microorganisms interact to determine the capacity of ecosystems to provide multiple functions simultaneously (multifunctionality) under climate change is poorly known. We conducted a common garden experiment using grassland species to evaluate how plant functional structure and soil microbial (bacteria and protists) diversity and abundance regulate soil multifunctionality responses to joint changes in plant species richness (one, three and six species) and simulated climate change (3°C warming and 35% rainfall reduction). The effects of species richness and climate on soil multifunctionality were indirectly driven via changes in plant functional structure and their relationships with the abundance and diversity of soil bacteria and protists. More specifically, warming selected for the larger and most productive plant species, increasing the average size within communities and leading to reductions in functional plant diversity. These changes increased the total abundance of bacteria that, in turn, increased that of protists, ultimately promoting soil multifunctionality. Our work suggests that cascading effects between plant functional traits and the abundance of multitrophic soil organisms largely regulate the response of soil multifunctionality to simulated climate change, and ultimately provides novel experimental insights into the mechanisms underlying the effects of biodiversity and climate change on ecosystem functioning.
Biogeochemical processes and ecosystemic functions are mostly driven by soil microbial communities. However, most methods focus on evaluating the total microbial community and fail to discriminate its active fraction which is linked to soil functionality. Precisely, the activity of the microbial community is strongly limited by the availability of organic carbon (C) in soils under arid and semi-arid climate. Here, we provide a complementary genomic and metaproteomic approach to investigate the relationships between the diversity of the total community, the active diversity and ecosystem functionality across a dissolved organic carbon (DOC) gradient in southeast Spain. DOC correlated with the ecosystem multifunctionality index composed by soil respiration, enzyme activities (urease, alkaline phosphatase and β-glucosidase) and microbial biomass (phospholipid fatty acids, PLFA). This study highlights that the active diversity (determined by metaprotoemics) but not the diversity of the whole microbial community (evaluated by amplicon gene sequencing) is related to the availability of organic C and it is also connected to the ecosystem multifunctionality index. We reveal that DOC shapes the activities of bacterial and fungal populations in Mediterranean semi-arid soils and determines the compartmentalization of functional niches. For instance, Rhizobales thrived at high-DOC sites probably fuelled by metabolism of one-C compounds. Moreover, the analysis of proteins involved in the transport and metabolism of carbohydrates revealed that Ascomycota and Basidiomycota occupied different nutritional niches. The functional mechanisms for niche specialization were not constant across the DOC gradient.
- MeSH
- biodiverzita * MeSH
- pentacyklické triterpeny MeSH
- půda chemie MeSH
- půdní mikrobiologie * MeSH
- uhlík chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Španělsko MeSH
Bacterial proteins exhibiting two or more unrelated functions, referred to as moonlighting proteins, are suggested to contribute to full virulence manifestation in pathogens. An expanding number of published studies have revealed the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to be a multitasking protein with virulence impact in a number of pathogenic bacteria. This protein can be detected on the bacterial surface or outside the bacterial cell, where it interacts with host proteins. In this way, GAPDH is able to modulate various pathogenic processes. Moreover, it has been shown to be involved in non-enzymatic processes inside the bacterial cell. In this mini review, we summarize main findings concerning the multiple localization and protein interactions of GAPDH derived from bacterial pathogens of humans. We also briefly discuss problems associated with using GAPDH as a vaccine antigen and endeavor to inspire further research to fill gaps in the existing knowledge.
- MeSH
- Bacteria enzymologie patogenita MeSH
- bakteriální infekce mikrobiologie prevence a kontrola MeSH
- bakteriální proteiny metabolismus MeSH
- bakteriální vakcíny imunologie MeSH
- glyceraldehyd-3-fosfátdehydrogenasy imunologie metabolismus MeSH
- lidé MeSH
- proteiny metabolismus MeSH
- vazba proteinů MeSH
- virulence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Climate change will affect semiarid ecosystems through severe droughts that increase the competition for resources in plant and microbial communities. In these habitats, adaptations to climate change may consist of thinning-that reduces competition for resources through a decrease in tree density and the promotion of plant survival. We deciphered the functional and phylogenetic responses of the microbial community to 6 years of drought induced by rainfall exclusion and how forest management affects its resistance to drought, in a semiarid forest ecosystem dominated by Pinus halepensis Mill. A multiOMIC approach was applied to reveal novel, community-based strategies in the face of climate change. The diversity and the composition of the total and active soil microbiome were evaluated by 16S rRNA gene (bacteria) and ITS (fungal) sequencing, and by metaproteomics. The microbial biomass was analyzed by phospholipid fatty acids (PLFAs), and the microbially mediated ecosystem multifunctionality was studied by the integration of soil enzyme activities related to the cycles of C, N, and P. The microbial biomass and ecosystem multifunctionality decreased in drought-plots, as a consequence of the lower soil moisture and poorer plant development, but this decrease was more notable in unthinned plots. The structure and diversity of the total bacterial community was unaffected by drought at phylum and order level, but did so at genus level, and was influenced by seasonality. However, the total fungal community and the active microbial community were more sensitive to drought and were related to ecosystem multifunctionality. Thinning in plots without drought increased the active diversity while the total diversity was not affected. Thinning promoted the resistance of ecosystem multifunctionality to drought through changes in the active microbial community. The integration of total and active microbiome analyses avoids misinterpretations of the links between the soil microbial community and climate change.
The Entner-Doudoroff pathway (ED-P) was established in 2016 as the fourth glycolytic pathway in Synechocystis sp. PCC 6803. ED-P consists of two reactions, the first catalyzed by 6-phosphogluconate dehydratase (EDD), the second by keto3-deoxygluconate-6-phosphate aldolase/4-hydroxy-2-oxoglutarate aldolase (EDA). ED-P was previously concluded to be a widespread (∼92%) pathway among cyanobacteria, but current bioinformatic analysis estimated the occurrence of ED-P to be either scarce (∼1%) or uncommon (∼47%), depending if dihydroxy-acid dehydratase (ilvD) also functions as EDD (currently assumed). Thus, the biochemical characterization of ilvD is a task pending to resolve this uncertainty. Next, we have provided new insights into several single and double glycolytic mutants based on kinetic model of central carbon metabolism of Synechocystis. The model predicted that silencing 6-phosphogluconate dehydrogenase (gnd) could be coupled with ∼90% down-regulation of G6P-dehydrogenase, also limiting the metabolic flux via ED-P. Furthermore, our metabolic flux estimation implied that growth impairment linked to silenced EDA under mixotrophic conditions is not caused by diminished carbon flux via ED-P but rather by a missing mechanism related to the role of EDA in metabolism. We proposed two possible, mutually non-exclusive explanations: (i) Δeda leads to disrupted carbon catabolite repression, regulated by 2-keto3-deoxygluconate-6-phosphate (ED-P intermediate), and (ii) EDA catalyzes the interconversion between glyoxylate and 4-hydroxy-2-oxoglutarate + pyruvate in the proximity of TCA cycle, possibly effecting the levels of 2-oxoglutarate under Δeda. We have also proposed a new pathway from EDA toward proline, which could explain the proline accumulation under Δeda. In addition, the presented in silico method provides an alternative to 13C metabolic flux analysis for marginal metabolic pathways around/below the threshold of ultrasensitive LC-MS. Finally, our in silico analysis provided alternative explanations for the role of ED-P in Synechocystis while identifying some severe uncertainties.
- Publikační typ
- časopisecké články MeSH
Over the recent decades, hyperbranched polymers have received much attention in both academic and industrial sphere. Due to their highly branched structure and multifunctionality, hyperbranched polymers exhibit unique chemical and physical properties. Many hyperbranched polymers have been prepared by one-step polymerization. The polymerizations can be divided into three categories: step-growth polycondensation of ABx monomers, selfcondensative vinyl polymerization of AB* monomers and branching ring-opening polymerization of hypothetical ABx monomers. This review highlights some examples of synthesis of the most important hyperbranched polymers. Special attention is paid to step-growth polycondensation of ABx-type monomers and to polycondensation of A2 and B3 monomers. Some properties of hyperbranched polymers and their potential applications are also described.
The rise of antibiotic resistance necessitates the development of innovative antimicrobial strategies. Antimicrobial peptides (AMPs), with their broad-spectrum activity and membrane-targeting mechanisms, offer an attractive alternative to conventional antibiotics but are limited by toxicity, proteolytic instability, and production costs. In this study, we report a series of novel AMP mimics combining cationic di- and tripeptides with cobalt bis(dicarbollide) (COSAN) and its iodinated analogue (I-COSAN). These metallacarborane-peptide hybrids retained the amphiphilic structure of AMPs and demonstrated potent, broad-spectrum antibacterial activity while exhibiting low hemolytic activity and cytotoxicity. Mechanistically, the best-performing conjugate induced bacterial membrane depolarization without cell lysis, accompanied by ATP depletion, reactive oxygen species overproduction, and morphological changes. Importantly, the conjugates resisted proteolytic degradation, demonstrating that a modification with a metallacarborane combines biological activity with enhanced stability. These findings introduce metallacarborane-peptide hybrids as a versatile platform for developing next-generation antimicrobials that combine the multifunctionality of AMPs with improved stability.
- MeSH
- antibakteriální látky * farmakologie chemie chemická syntéza MeSH
- hemolýza účinky léků MeSH
- lidé MeSH
- membránové potenciály * účinky léků MeSH
- mikrobiální testy citlivosti MeSH
- proteolýza MeSH
- reaktivní formy kyslíku metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
