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Detecting and prioritizing biosynthetic gene clusters for bioactive compounds in bacteria and fungi.Applied Microbiology and Biotechnology Apr 2019Secondary metabolites (SM) produced by fungi and bacteria have long been of exceptional interest owing to their unique biomedical ramifications. The traditional... (Review)
Review
Secondary metabolites (SM) produced by fungi and bacteria have long been of exceptional interest owing to their unique biomedical ramifications. The traditional discovery of new natural products that was mainly driven by bioactivity screening has now experienced a fresh new approach in the form of genome mining. Several bioinformatics tools have been continuously developed to detect potential biosynthetic gene clusters (BGCs) that are responsible for the production of SM. Although the principles underlying the computation of these tools have been discussed, the biological background is left underrated and ambiguous. In this review, we emphasize the biological hypotheses in BGC formation driven from the observations across genomes in bacteria and fungi, and provide a comprehensive list of updated algorithms/tools exclusively for BGC detection. Our review points to a direction that the biological hypotheses should be systematically incorporated into the BGC prediction and assist the prioritization of candidate BGC.
Topics: Bacteria; Biological Products; Computational Biology; Drug Resistance, Microbial; Fungi; Gene Duplication; Gene Transfer, Horizontal; Genome, Microbial; Multigene Family; Secondary Metabolism
PubMed: 30859257
DOI: 10.1007/s00253-019-09708-z -
Genome Medicine Nov 2015The human microbiome, often referred to as the 'second genome', encompasses up to 100-fold more genes than the host genome. In contrast to the human genome, the... (Review)
Review
The human microbiome, often referred to as the 'second genome', encompasses up to 100-fold more genes than the host genome. In contrast to the human genome, the microbial genome is flexible and amenable to change during the host's lifetime. As the composition of the microbial metagenome has been associated with the development of human disease, the mechanisms controlling the composition and function of the metagenome are of considerable interest and therapeutic potential. In the past few years, studies have revealed how the host immune system is involved in determining the microbial metagenome, and, in turn, how the microbiota regulates gene expression in the immune system. This species-specific bidirectional interaction is required for homeostatic health, whereas aberrations in the tightly controlled regulatory circuits that link the host immunogenome and the microbial metagenome drive susceptibility to common human diseases. Here, we summarize some of the major principles orchestrating this cross-talk between microbial and host genomes, with a special focus on the interaction between the intestinal immune system and the gut microbiome. Understanding the reciprocal genetic and epigenetic control between host and microbiota will be an important step towards the development of novel therapies against microbiome-driven diseases.
Topics: Animals; Gastrointestinal Tract; Gene Expression Regulation; Genome, Microbial; Humans; Immune System; Immune System Diseases; Metagenomics; Microbiota
PubMed: 26589591
DOI: 10.1186/s13073-015-0249-9 -
Nature Communications May 2024Heliorhodopsins (HeRs) have been hypothesized to have widespread functions. Recently, the functions for few HeRs have been revealed; however, the hypothetical functions...
Heliorhodopsins (HeRs) have been hypothesized to have widespread functions. Recently, the functions for few HeRs have been revealed; however, the hypothetical functions remain largely unknown. Herein, we investigate light-modulation of heterodimeric multidrug resistance ATP-binding cassette transporters (OmrDE) mediated by Omithinimicrobium cerasi HeR. In this study, we classifiy genes flanking the HeR-encoding genes and identify highly conservative residues for protein-protein interactions. Our results reveal that the interaction between OcHeR and OmrDE shows positive cooperatively sequential binding through thermodynamic parameters. Moreover, light-induced OcHeR upregulates OmrDE drug transportation. Hence, the binding may be crucial to drug resistance in O. cerasi as it survives in a drug-containing habitat. Overall, we unveil a function of HeR as regulatory rhodopsin for multidrug resistance. Our findings suggest potential applications in optogenetic technology.
Topics: ATP-Binding Cassette Transporters; Light; Bacterial Proteins; Protein Binding; Rhodopsins, Microbial; Optogenetics
PubMed: 38773114
DOI: 10.1038/s41467-024-48650-1 -
Genome Biology Nov 2014Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of... (Review)
Review
Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional 'line lists' (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.
Topics: Base Sequence; Chromosome Mapping; Communicable Diseases; Genome, Microbial; Genome, Viral; Genomics; High-Throughput Nucleotide Sequencing; Humans; Public Health
PubMed: 25418119
DOI: 10.1186/s13059-014-0538-4 -
Cell Mar 2018
Topics: Bacillus Phages; Bacillus subtilis; DNA, Viral; Genetics, Microbial; Sigma Factor; Templates, Genetic
PubMed: 29522732
DOI: 10.1016/j.cell.2018.02.041 -
Plant Physiology Oct 2021Microbial rhodopsins have advanced optogenetics since the discovery of channelrhodopsins almost two decades ago. During this time an abundance of microbial rhodopsins... (Review)
Review
Microbial rhodopsins have advanced optogenetics since the discovery of channelrhodopsins almost two decades ago. During this time an abundance of microbial rhodopsins has been discovered, engineered, and improved for studies in neuroscience and other animal research fields. Optogenetic applications in plant research, however, lagged largely behind. Starting with light-regulated gene expression, optogenetics has slowly expanded into plant research. The recently established all-trans retinal production in plants now enables the use of many microbial opsins, bringing extra opportunities to plant research. In this review, we summarize the recent advances of rhodopsin-based plant optogenetics and provide a perspective for future use, combined with fluorescent sensors to monitor physiological parameters.
Topics: Biosensing Techniques; Fluorescent Dyes; Molecular Imaging; Optogenetics; Plant Physiological Phenomena; Plants; Rhodopsin; Rhodopsins, Microbial
PubMed: 35237820
DOI: 10.1093/plphys/kiab338 -
FEMS Microbiology Reviews Mar 2017High individuality, large complexity and limited understanding of the mechanisms underlying human intestinal microbiome function remain the major challenges for... (Review)
Review
High individuality, large complexity and limited understanding of the mechanisms underlying human intestinal microbiome function remain the major challenges for designing beneficial modulation strategies. Exemplified by the analysis of intestinal bacteria in a thousand Western adults, we discuss key concepts of the human intestinal microbiome landscape, i.e. the compositional and functional 'core', the presence of community types and the existence of alternative stable states. Genomic investigation of core taxa revealed functional redundancy, which is expected to stabilize the ecosystem, as well as taxa with specialized functions that have the potential to shape the microbiome landscape. The contrast between Prevotella- and Bacteroides-dominated systems has been well described. However, less known is the effect of not so abundant bacteria, for example, Dialister spp. that have been proposed to exhibit distinct bistable dynamics. Studies employing time-series analysis have highlighted the dynamical variation in the microbiome landscape with and without the effect of defined perturbations, such as the use of antibiotics or dietary changes. We incorporate ecosystem-level observations of the human intestinal microbiota and its keystone species to suggest avenues for designing microbiome modulation strategies to improve host health.
Topics: Bacteria; Biodiversity; Ecosystem; Gastrointestinal Microbiome; Genome, Microbial; Humans; Intestines
PubMed: 28364729
DOI: 10.1093/femsre/fuw045 -
MSystems Aug 2023Stable isotope probing (SIP) facilitates culture-independent identification of active microbial populations within complex ecosystems through isotopic enrichment of...
Stable isotope probing (SIP) facilitates culture-independent identification of active microbial populations within complex ecosystems through isotopic enrichment of nucleic acids. Many DNA-SIP studies rely on 16S rRNA gene sequences to identify active taxa, but connecting these sequences to specific bacterial genomes is often challenging. Here, we describe a standardized laboratory and analysis framework to quantify isotopic enrichment on a per-genome basis using shotgun metagenomics instead of 16S rRNA gene sequencing. To develop this framework, we explored various sample processing and analysis approaches using a designed microbiome where the identity of labeled genomes and their level of isotopic enrichment were experimentally controlled. With this ground truth dataset, we empirically assessed the accuracy of different analytical models for identifying active taxa and examined how sequencing depth impacts the detection of isotopically labeled genomes. We also demonstrate that using synthetic DNA internal standards to measure absolute genome abundances in SIP density fractions improves estimates of isotopic enrichment. In addition, our study illustrates the utility of internal standards to reveal anomalies in sample handling that could negatively impact SIP metagenomic analyses if left undetected. Finally, we present , an R package to facilitate the estimation of absolute abundances and perform statistical analyses for identifying labeled genomes within SIP metagenomic data. This experimentally validated analysis framework strengthens the foundation of DNA-SIP metagenomics as a tool for accurately measuring the activity of environmental microbial populations and assessing their genomic potential. IMPORTANCE Answering the questions, and within complex microbial communities is paramount for our ability to model, predict, and modulate microbiomes for improved human and planetary health. These questions can be pursued using stable isotope probing to track the incorporation of labeled compounds into cellular DNA during microbial growth. However, with traditional stable isotope methods, it is challenging to establish links between an active microorganism's taxonomic identity and genome composition while providing quantitative estimates of the microorganism's isotope incorporation rate. Here, we report an experimental and analytical workflow that lays the foundation for improved detection of metabolically active microorganisms and better quantitative estimates of genome-resolved isotope incorporation, which can be used to further refine ecosystem-scale models for carbon and nutrient fluxes within microbiomes.
Topics: Humans; Metagenomics; RNA, Ribosomal, 16S; DNA; Isotopes; Microbiota
PubMed: 37377419
DOI: 10.1128/msystems.01280-22 -
The ISME Journal Nov 2023A major challenge in managing and engineering microbial communities is determining whether and how microbial community responses to environmental alterations can be...
A major challenge in managing and engineering microbial communities is determining whether and how microbial community responses to environmental alterations can be predicted and explained, especially in microorganism-driven systems. We addressed this challenge by monitoring microbial community responses to the periodic addition of the same feedstock throughout anaerobic digestion, a typical microorganism-driven system where microorganisms degrade and transform the feedstock. The immediate and delayed response consortia were assemblages of microorganisms whose abundances significantly increased on the first or third day after feedstock addition. The immediate response consortia were more predictable than the delayed response consortia and showed a reproducible and predictable order-level composition across multiple feedstock additions. These results stood in both present (16 S rRNA gene) and potentially active (16 S rRNA) microbial communities and in different feedstocks with different biodegradability and were validated by simulation modeling. Despite substantial species variability, the immediate response consortia aligned well with the reproducible CH production, which was attributed to the conservation of expressed functions by the response consortia throughout anaerobic digestion, based on metatranscriptomic data analyses. The high species variability might be attributed to intraspecific competition and contribute to biodiversity maintenance and functional redundancy. Our results demonstrate reproducible and predictable microbial community responses and their importance in stabilizing system functions.
Topics: Anaerobiosis; Microbiota; Biodiversity; RNA, Ribosomal, 16S; RNA, Ribosomal; Bioreactors; Microbial Consortia
PubMed: 37666974
DOI: 10.1038/s41396-023-01505-x -
ILAR Journal Oct 2020Our bodies and those of our animal research subjects are colonized by bacterial communities that occupy virtually every organ system, including many previously...
Our bodies and those of our animal research subjects are colonized by bacterial communities that occupy virtually every organ system, including many previously considered sterile. These bacteria reside as complex communities that are collectively referred to as microbiota. Prior to the turn of the century, characterization of these communities was limited by a reliance on culture of organisms on a battery of selective media. It was recognized that the vast majority of microbes, especially those occupying unique niches of the body such as the anaerobic environment of the intestinal tract, were uncultivatable. However, with the onset and advancement of next-generation sequencing technology, we are now capable of characterizing these complex communities without the need to cultivate, and this has resulted in an explosion of information and new challenges in interpreting data generated about, and in the context of, these complex communities. We have long known that these microbial communities often exist in an intricate balance that, if disrupted (ie, dysbiosis), can lead to disease or increased susceptibility to disease. Because of many functional redundancies, the makeup of these colonies can vary dramatically within healthy individuals [1]. However, there is growing evidence that subtle differences can alter the phenotype of various animal models, which may translate to the varying susceptibility to disease seen in the human population. In this manuscript, we discuss how to include complex microbiota as a consideration in experimental design and model reproducibility and how to exploit the extensive variation that exists in contemporary rodent research colonies. Our focus will be the intestinal or gut microbiota (GM), but it should be recognized that microbial communities exist in many other body compartments and these too likely influence health and disease [2, 3]. Much like host genetics, can we one day harness the vast genetic capacity of the microbes we live with in ways that will benefit human and animal health?
Topics: Animals; Gastrointestinal Microbiome; Genome, Microbial; Humans; Models, Animal
PubMed: 32706377
DOI: 10.1093/ilar/ilaa011