scholarly journals Biogeography of Bacterial Communities and Specialized Metabolism in Human Aerodigestive Tract Microbiomes

2021 ◽  
Author(s):  
Reed M. Stubbendieck ◽  
Susan E. Zelasko ◽  
Nasia Safdar ◽  
Cameron R. Currie
Keyword(s):  
Bacterial Communities ◽  
Biological Activities ◽  
Human Microbiome ◽  
Aerodigestive Tract ◽  
Specialized Metabolism ◽  
Specialized Metabolites

Bacteria produce specialized metabolites to compete with other microbes. Though the biological activities of many specialized metabolites have been determined, our understanding of their ecology is limited, particularly within the human microbiome.

scholarly journals Activity throughout the lichen phylogeny indicates a focus on regulation of specialized metabolites

2020 ◽  
Author(s):  
Ludmila V. Roze ◽  
Maris Laivenieks ◽  
Kristi Gdanetz ◽  
John E. Linz ◽  
Alan M. Fryday ◽  
...  
Keyword(s):  
Biological Activities ◽  
Small Sample Size ◽  
Close Association ◽  
Small Sample ◽  
Lichen Species ◽  
Specialized Metabolism ◽  
Specialized Metabolites ◽  
Lichen Community ◽  
Interesting Study

AbstractLichens are complex multi-microorganismal communities that have evolved the ability to share their thalli with a variety of microorganisms. As such, the lichenized fungus becomes a scaffold for a variety of microbes and occasionally insects. Lichens are known to produce a plethora of unique specialized (secondary) compounds that demonstrate biological activities, including antibacterial, antifungal, antiviral, and antioxidant, that may provide protection from harmful microbes. The longevity of lichens and their robustness, despite a close association with diverse microbes, provides an interesting study system to view the role of specialized metabolites in managing a microbial community. The objective of this study was to identify the effects lichens may have on basic functions of fungi in and on the lichens. We tested chemical extracts from lichen species across the phylogenetic tree for their effects on sporulation, hyphal growth and specialized metabolite production, using two well-studied mycotoxigenic fungi (Aspergillus parasiticus (aflatoxin) and Fusarium graminearum (trichothecenes) whose functions are easily observed in culture. By far the most prevalent activity among the 67 lichens we tested were effects on accumulation of fungal specialized metabolites, which appeared in 92% of the lichen species analyzed across the phylogeny, although the lichen extracts were also active against fungal sporulation (31%) and growth (12%). The consistent presence of this regulatory activity for specialized metabolism indicates this is an important aspect of lichen integrity. Interestingly, inhibition of accumulation of products of the aflatoxin biosynthetic pathway was the predominant activity, whereas increased accumulation versus decreased accumulation of the production of trichothecenes were about equal. This suggests multiple mechanisms for addressing fungal processes. We performed microbiome analysis of four lichen species and identified oomycetes as members of the microbiomes. Although a small sample size was used for comparing microbiomes, the lichen species exhibiting lower effects on the test fungi had a higher number of OTUs. Members of the lichen community may manipulate specialized metabolism of the essential and transient fungal members and thus attenuate negative interactions with the incumbent fungi or, alternatively, may support the production of compounds by beneficial fungal partners. The ability to control the microbiome by specialized metabolites as opposed to controlling by reducing sporulation of growth, can be effective, discerning, and energetically thrifty, allowing the microbiome members to be controlled without being invasive. Elucidating the role of specialized metabolites in the mechanisms underlying lichen assembly and function has important implications for understanding not only lichen community assembly but for revealing the fundamental processes in microbiota in general.

Control of Specialized Metabolism by Signaling and Transcriptional Regulation: Opportunities for New Platforms for Drug Discovery?

2018 ◽  
Vol 72 (1) ◽  
pp. 25-48 ◽  
Author(s):  
M. Daniel-Ivad ◽  
S. Pimentel-Elardo ◽  
J.R. Nodwell
Keyword(s):  
Small Molecules ◽  
Biological Activities ◽  
Mechanisms Of Action ◽  
Nutrient Sensing ◽  
Living Systems ◽  
Regulatory Mechanisms ◽  
Environmental Cues ◽  
Dense Network ◽  
Specialized Metabolism ◽  
Specialized Metabolites

Specialized metabolites are bacterially produced small molecules that have an extraordinary diversity of important biological activities. They are useful as biochemical probes of living systems, and they have been adapted for use as drugs for human afflictions ranging from infectious diseases to cancer. The biosynthetic genes for these molecules are controlled by a dense network of regulatory mechanisms: Cell-cell signaling and nutrient sensing are conspicuous features of this network. While many components of these mechanisms have been identified, important questions about their biological roles remain shrouded in mystery. In addition to identifying new molecules and solving their mechanisms of action (a central preoccupation in this field), we suggest that addressing questions of quorum sensing versus diffusion sensing and identifying the dominant nutritional and environmental cues for specialized metabolism are important directions for research.

scholarly journals Analysis of the Upper Respiratory Tract Microbiotas as the Source of the Lung and Gastric Microbiotas in Healthy Individuals

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Christine M. Bassis ◽  
John R. Erb-Downward ◽  
Robert P. Dickson ◽  
Christine M. Freeman ◽  
Thomas M. Schmidt ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Nasal Cavity ◽  
Bacterial Communities ◽  
Healthy Subjects ◽  
Aerodigestive Tract ◽  
Oral Microbiome ◽  
Gastric Aspirate ◽  
Upper Respiratory Tract ◽  
Healthy Individuals ◽  
Lung Microbiome

ABSTRACTNo studies have examined the relationships between bacterial communities along sites of the upper aerodigestive tract of an individual subject. Our objective was to perform an intrasubject and intersite analysis to determine the contributions of two upper mucosal sites (mouth and nose) as source communities for the bacterial microbiome of lower sites (lungs and stomach). Oral wash, bronchoalveolar lavage (BAL) fluid, nasal swab, and gastric aspirate samples were collected from 28 healthy subjects. Extensive analysis of controls and serial intrasubject BAL fluid samples demonstrated that sampling of the lungs by bronchoscopy was not confounded by oral microbiome contamination. By quantitative PCR, the oral cavity and stomach contained the highest bacterial signal levels and the nasal cavity and lungs contained much lower levels. Pyrosequencing of 16S rRNA gene amplicon libraries generated from these samples showed that the oral and gastric compartments had the greatest species richness, which was significantly greater in both than the richness measured in the lungs and nasal cavity. The bacterial communities of the lungs were significantly different from those of the mouth, nose, and stomach, while the greatest similarity was between the oral and gastric communities. However, the bacterial communities of healthy lungs shared significant membership with the mouth, but not the nose, and marked subject-subject variation was noted. In summary, microbial immigration from the oral cavity appears to be the significant source of the lung microbiome during health, but unlike the stomach, the lungs exhibit evidence of selective elimination of Prevotella bacteria derived from the upper airways.IMPORTANCEWe have demonstrated that the bacterial communities of the healthy lung overlapped those found in the mouth but were found at lower concentrations, with lower membership and a different community composition. The nasal microbiome, which was distinct from the oral microbiome, appeared to contribute little to the composition of the lung microbiome in healthy subjects. Our studies of the nasal, oral, lung, and stomach microbiomes within an individual illustrate the microbiological continuity of the aerodigestive tract in healthy adults and provide culture-independent microbiological support for the concept that microaspiration is common in healthy individuals.

scholarly journals Bacterial communities of cryoconite holes of a temperate alpine glacier show both seasonal trends and year-to-year variability

2018 ◽  
Vol 59 (77) ◽  
pp. 1-9 ◽  
Author(s):  
Francesca Pittino ◽  
Maurizio Maglio ◽  
Isabella Gandolfi ◽  
Roberto Sergio Azzoni ◽  
Guglielmina Diolaiuti ◽  
...  
Keyword(s):  
Hot Spots ◽  
Bacterial Communities ◽  
Biological Activities ◽  
Meteorological Data ◽  
Rrna Gene ◽  
Ecological Communities ◽  
Italian Alps ◽  
Glacier Surface ◽  
Alpine Glacier ◽  
Cryoconite Hole

ABSTRACTCryoconite holes are small depressions of the glacier surface filled with melting water and with a wind-blown debris on the bottom. These environments are considered hot spots of biodiversity and biological activities on glaciers and host communities dominated by bacteria. Most of the studies on cryoconite holes assume that their communities are stable. However, evidence of seasonal variation in cryoconite hole ecological communities exists. We investigated the variation of the bacterial communities of cryoconite holes of Forni Glacier (Central Italian Alps) during the melting seasons (July–September) 2013 and 2016, for which samples at three and five time-points, respectively were available. Bacterial communities were characterized by high-throughput Illumina sequencing of the hypervariable V5−V6 regions of 16S rRNA gene, while meteorological data were obtained by an automatic weather station. We found consistent trends in bacterial communities, which shifted from cyanobacteria-dominated communities in July to communities dominated by heterotrophic orders in late August and September. Temperature seems also to affect seasonal dynamics of communities. We also compared bacterial communities at the beginning of the melting season across 4 years (2012, 2013, 2015 and 2016) and found significant year-to-year variability. Cryoconite hole communities on temperate glaciers are therefore not temporally stable.

scholarly journals Multiplex Genome Editing in Yeast by CRISPR/Cas9 – A Potent and Agile Tool to Reconstruct Complex Metabolic Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Joseph Christian Utomo ◽  
Connor Lorne Hodgins ◽  
Dae-Kyun Ro
Keyword(s):  
Genome Editing ◽  
Metabolic Pathways ◽  
Functional Characterization ◽  
Primary Metabolism ◽  
Biosynthetic Pathways ◽  
Post Translational Modification ◽  
Precise Integration ◽  
Specialized Metabolism ◽  
Specialized Metabolites ◽  
Plant Specialized Metabolism

Numerous important pharmaceuticals and nutraceuticals originate from plant specialized metabolites, most of which are synthesized via complex biosynthetic pathways. The elucidation of these pathways is critical for the applicable uses of these compounds. Although the rapid progress of the omics technology has revolutionized the identification of candidate genes involved in these pathways, the functional characterization of these genes remains a major bottleneck. Baker’s yeast (Saccharomyces cerevisiae) has been used as a microbial platform for characterizing newly discovered metabolic genes in plant specialized metabolism. Using yeast for the investigation of numerous plant enzymes is a streamlined process because of yeast’s efficient transformation, limited endogenous specialized metabolism, partially sharing its primary metabolism with plants, and its capability of post-translational modification. Despite these advantages, reconstructing complex plant biosynthetic pathways in yeast can be time intensive. Since its discovery, CRISPR/Cas9 has greatly stimulated metabolic engineering in yeast. Yeast is a popular system for genome editing due to its efficient homology-directed repair mechanism, which allows precise integration of heterologous genes into its genome. One practical use of CRISPR/Cas9 in yeast is multiplex genome editing aimed at reconstructing complex metabolic pathways. This system has the capability of integrating multiple genes of interest in a single transformation, simplifying the reconstruction of complex pathways. As plant specialized metabolites usually have complex multigene biosynthetic pathways, the multiplex CRISPR/Cas9 system in yeast is suited well for functional genomics research in plant specialized metabolism. Here, we review the most advanced methods to achieve efficient multiplex CRISPR/Cas9 editing in yeast. We will also discuss how this powerful tool has been applied to benefit the study of plant specialized metabolism.

scholarly journals Robust predictions of specialized metabolism genes through machine learning

2018 ◽  
Author(s):  
Bethany M. Moore ◽  
Peipei Wang ◽  
Pengxiang Fan ◽  
Bryan Leong ◽  
Craig A. Schenck ◽  
...  
Keyword(s):  
Machine Learning ◽  
Prediction Model ◽  
Gene Networks ◽  
Experimental Studies ◽  
Plant Genome ◽  
Primary Metabolism ◽  
Specialized Metabolism ◽  
Specialized Metabolites ◽  
General Metabolism ◽  
Pattern Sequence

AbstractPlant specialized metabolism (SM) enzymes produce lineage-specific metabolites with important ecological, evolutionary, and biotechnological implications. Using Arabidopsis thaliana as a model, we identified distinguishing characteristics of SM and GM (general metabolism, traditionally referred to as primary metabolism) genes through a detailed study of features including duplication pattern, sequence conservation, transcription, protein domain content, and gene network properties. Analysis of multiple sets of benchmark genes revealed that SM genes tend to be tandemly duplicated, co-expressed with their paralogs, narrowly expressed at lower levels, less conserved, and less well connected in gene networks relative to GM genes. Although the values of each of these features significantly differed between SM and GM genes, any single feature was ineffective at predicting SM from GM genes. Using machine learning methods to integrate all features, a well performing prediction model was established with a true positive rate of 0.87 and a true negative rate of 0.71. In addition, 86% of known SM genes not used to create the machine learning model were predicted as SM genes, further demonstrating its accuracy. We also demonstrated that the model could be further improved when we distinguished between SM, GM, and junction genes responsible for reactions shared by SM and GM pathways. Application of the prediction model led to the identification of 1,217 A. thaliana genes with previously unknown functions, providing a global, high-confidence estimate of SM gene content in a plant genome.SignificanceSpecialized metabolites are critical for plant-environment interactions, e.g., attracting pollinators or defending against herbivores, and are important sources of plant-based pharmaceuticals. However, it is unclear what proportion of enzyme-encoding genes play roles in specialized metabolism (SM) as opposed to general metabolism (GM) in any plant species. This is because of the diversity of specialized metabolites and the considerable number of incompletely characterized pathways responsible for their production. In addition, SM gene ancestors frequently played roles in GM. We evaluate features distinguishing SM and GM genes and build a computational model that accurately predicts SM genes. Our predictions provide candidates for experimental studies, and our modeling approach can be applied to other species that produce medicinally or industrially useful compounds.

scholarly journals Within and cross species predictions of plant specialized metabolism genes using transfer learning

2020 ◽  
Author(s):  
Bethany M. Moore ◽  
Peipei Wang ◽  
Pengxiang Fan ◽  
Aaron Lee ◽  
Bryan Leong ◽  
...  
Keyword(s):  
Transfer Learning ◽  
Prediction Models ◽  
Learning Strategy ◽  
Model Species ◽  
Specialized Metabolism ◽  
Specialized Metabolites ◽  
General Metabolism ◽  
Model Predictions ◽  
Gene Functions ◽  
F Measure

AbstractPlant specialized metabolites mediate interactions between plants and the environment and have significant agronomical/pharmaceutical value. Most genes involved in specialized metabolism (SM) are unknown because of the large number of metabolites and the challenge in differentiating SM genes from general metabolism (GM) genes. Plant models like Arabidopsis thaliana have extensive, experimentally derived annotations, whereas many non-model species do not. Here we employed a machine learning strategy, transfer learning, where knowledge from A. thaliana is transferred to predict gene functions in cultivated tomato with fewer experimentally annotated genes. The first tomato SM/GM prediction model using only tomato data performs well (F-measure=0.74, compared with 0.5 for random and 1.0 for perfect predictions), but from manually curating 88 SM/GM genes, we found many mis-predicted entries were likely mis-annotated. When the SM/GM prediction models built with A. thaliana data were used to filter out genes where the A. thaliana-based model predictions disagreed with tomato annotations, the new tomato model trained with filtered data improved significantly (F-measure=0.92). Our study demonstrates that SM/GM genes can be better predicted by leveraging cross-species information. Additionally, our findings provide an example for transfer learning in genomics where knowledge can be transferred from an information-rich species to an information-poor one.

scholarly journals Tomato roots secrete tomatine to modulate the bacterial assemblage of the rhizosphere

2021 ◽  
Author(s):  
Masaru Nakayasu ◽  
Kohei Ohno ◽  
Kyoko Takamatsu ◽  
Yuichi Aoki ◽  
Shinichi Yamazaki ◽  
...  
Keyword(s):  
Bacterial Communities ◽  
Plant Pathogens ◽  
Biological Activities ◽  
Growth Stages ◽  
Ethylene Response Factor ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Bacterial Assemblage ◽  
Hydroponically Grown

Abstract Saponins are the group of plant specialized metabolites which are widely distributed in angiosperm plants and have various biological activities. The present study focused on α-tomatine, a major saponin present in tissues of tomato (Solanum lycopersicum) plants. α-Tomatine is responsible for defense against plant pathogens and herbivores, but its biological function in the rhizosphere remains unknown. Secretion of tomatine was higher at the early growth than the green-fruit stage in hydroponically grown plants, and the concentration of tomatine in the rhizosphere of field-grown plants was higher than that of the bulk soil at all growth stages. The effects of tomatine and its aglycone tomatidine on the bacterial communities in the soil were evaluated in vitro, revealing that both compounds influenced the microbiome in a concentration-dependent manner. Numerous bacterial families were influenced in tomatine/tomatidine-treated soil as well as in the tomato rhizosphere. Sphingomonadaceae species, which are commonly observed and enriched in tomato rhizospheres in the fields, were also enriched in tomatine- and tomatidine-treated soils. Moreover, a jasmonate-responsive ETHYLENE RESPONSE FACTOR 4 mutant associated with low tomatine production caused the root-associated bacterial communities to change with a reduced abundance of Sphingomonadaceae. Taken together, our results highlight the role of tomatine in shaping the bacterial communities of the rhizosphere and suggest additional functions of tomatine in belowground biological communication.

Rational engineering of specialized metabolites in bacteria and fungi

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ramsay Soup Teoua Kamdem ◽  
Omonike Ogbole ◽  
Pascal Wafo ◽  
F. Uzor Philip ◽  
Zulfiqar Ali ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Epigenetic Modification ◽  
Biological Activities ◽  
Specialized Metabolites ◽  
Rational Engineering ◽  
Powerful Approach ◽  
Extensive Range ◽  
Bacteria And Fungi ◽  
And Control ◽  
Improve Access

Abstract Bacteria and fungi have a high potential to produce compounds that display large structural change and diversity, thus displaying an extensive range of biological activities. Secondary metabolism or specialized metabolism is a term for pathways and small molecule products of metabolism that are not mandatory for the subsistence of the organism but improve and control their phenotype. Their interesting biological activities have occasioned their application in the fields of agriculture, food, and pharmaceuticals. Metabolic engineering is a powerful approach to improve access to these treasured molecules or to rationally engineer new ones. A thorough overview of engineering methods in secondary metabolism is presented, both in heterologous and epigenetic modification. Engineering methods to modify the structure of some secondary metabolite classes in their host are also intensively assessed.

scholarly journals Phytotoxicity of Schiekia timida Seed Extracts, a Mixture of Phenylphenalenones

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4197
Author(s):  
Fernanda Maria Marins Ocampos ◽  
Ana Julia Borim de Souza ◽  
Guilherme Medeiros Antar ◽  
Felipe Christoff Wouters ◽  
Luiz Alberto Colnago
Keyword(s):  
Chemical Composition ◽  
Methanolic Extract ◽  
Biological Activities ◽  
Germination Rate ◽  
Seed Extract ◽  
Hypocotyl Growth ◽  
Specialized Metabolites ◽  
Phytotoxic Effect ◽  
First Time ◽  
Seed Extracts

Phenylphenalenones, metabolites found in Schiekia timida (Haemodoraceae), are a class of specialized metabolites with many biological activities, being phytoalexins in banana plants. In the constant search to solve the problem of glyphosate and to avoid resistance to commercial herbicides, this work aimed to investigate the phytotoxic effect of the methanolic extract of S. timida seeds. The chemical composition of the seed extract was directly investigated by NMR and UPLC-QToF MS and the pre- and post-emergence phytotoxic effect on a eudicotyledonous model (Lactuca sativa) and a monocotyledonous model (Allium cepa) was evaluated through germination and seedling growth tests. Three concentrations of the extract (0.25, 0.50, and 1.00 mg/mL) were prepared, and four replicates for each of them were analyzed. Three major phenylphenalenones were identified by NMR spectroscopy: 4-hydroxy-anigorufone, methoxyanigorufone, and anigorufone, two of those reported for the first time in S. timida. The presence of seven other phenylphenalenones was suggested by the LC-MS analyses. The phenylphenalenone mixture did not affect the germination rate, but impaired radicle and hypocotyl growth on both models. The effect in the monocotyledonous model was statistically similar to glyphosate in the lowest concentration (0.25 mg/mL). Therefore, although more research on this topic is required to probe this first report, this investigation suggests for the first time that phenylphenalenone compounds may be post-emergence herbicides.

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