Emerging Applications of Bacteriocins as Antimicrobials,Anticancer Drugs,and Modulators of The Gastrointestinal Microbiota

The use of bacteriocins holds great promise in different areas such as health, food, nutrition, veterinary, nanotechnology, among others. Many research groups worldwide continue to advance the knowledge to unravel a novel range of therapeutic agents and food preservatives. This review addresses the advances of bacteriocins and their producer organisms as biocontrol agents for applications in the medical industry and agriculture. Furthermore, the bacteriocin mechanism of action and structural characteristics will be reviewed. Finally, the potential role of bacteriocins to modulate the signaling in host-associated microbial communities will be discussed.     

Exploring the Gastrointestinal “Nemabiome”: Deep Amplicon Sequencing to Quantify the Species Composition of Parasitic Nematode Communities

Parasitic helminth infections have a considerable impact on global human health as well as animal welfare and production. Although co-infection with multiple parasite species within a host is common, there is a dearth of tools with which to study the composition of these complex parasite communities. Helminth species vary in their pathogenicity, epidemiology and drug sensitivity and the interactions that occur between co-infecting species and their hosts are poorly understood. We describe the first application of deep amplicon sequencing to study parasitic nematode communities as well as introduce the concept of the gastro-intestinal “nemabiome”. The approach is analogous to 16S rDNA deep sequencing used to explore microbial communities, but utilizes the nematode ITS-2 rDNA locus instead. Gastro-intestinal parasites of cattle were used to develop the concept, as this host has many well-defined gastro-intestinal nematode species that commonly occur as complex co-infections. Further, the availability of pure mono-parasite populations from experimentally infected cattle allowed us to prepare mock parasite communities to determine, and correct for, species representation biases in the sequence data. We demonstrate that, once these biases have been corrected, accurate relative quantitation of gastro-intestinal parasitic nematode communities in cattle fecal samples can be achieved. We have validated the accuracy of the method applied to field-samples by comparing the results of detailed morphological examination of L3 larvae populations with those of the sequencing assay. The results illustrate the insights that can be gained into the species composition of parasite communities, using grazing cattle in the mid-west USA as an example. However, both the technical approach and the concept of the ‘nemabiome’ have a wide range of potential applications in human and veterinary medicine. These include investigations of host-parasite and parasite-parasite interactions during co-infection, parasite epidemiology, parasite ecology and the response of parasite populations to both drug treatments and control programs.     

Next-generation approaches to the microbial ecology of food fermentations

Food fermentations have enhanced human health since the dawn of time and remain a prevalent means of food processing and preservation. Due to their cultural and nutritional importance, many of these foods have been studied in detail using molecular tools, leading to enhancements in quality and safety. Furthermore, recent advances in high-throughput sequencing technology are revolutionizing the study of food microbial ecology, deepening insight into complex fermentation systems. This review provides insight into novel applications of select molecular techniques, particularly next-generation sequencing technology, for analysis of microbial communities in fermented foods. We present a guideline for integrated molecular analysis of food microbial ecology and a starting point for implementing next-generation analysis of food systems.     

Microbial ecology to manage processes in environmental biotechnology

Microbial ecology and environmental biotechnology are inherently tied to each other. The concepts and tools of microbial ecology are the basis for managing processes in environmental biotechnology; and these processes provide interesting ecosystems to advance the concepts and tools of microbial ecology. Revolutionary advancements in molecular tools to understand the structure and function of microbial communities are bolstering the power of microbial ecology. A push from advances in modern materials along with a pull from a societal need to become more sustainable is enabling environmental biotechnology to create novel processes. How do these two fields work together? Five principles illuminate the way: (i) aim for big benefits; (ii) develop and apply more powerful tools to understand microbial communities; (iii) follow the electrons; (iv) retain slow-growing biomass; and (v) integrate, integrate, integrate.     

Pre-genomic, genomic and post-genomic study of microbial communities involved in bioenergy

Microorganisms can produce renewable energy in large quantities and without damaging the environment or disrupting food supply. The microbial communities must be robust and self-stabilizing, and their essential syntrophies must be managed. Pre-genomic, genomic and post-genomic tools can provide crucial information about the structure and function of these microbial communities. Applying these tools will help accelerate the rate at which microbial bioenergy processes move from intriguing science to real-world practice.     

Population level virulence in polymicrobial communities associated with chronic disease

Renewed studies of chronic infection have shifted the focus from single pathogens to multi-microbial communities as culture-independent techniques reveal complex consortia of microbes associated with c...     

Protein-RNA interface residue prediction using machine learning: an assessment of the state of the art

Background

Understanding the interaction among different species within a community and their responses to environmental changes is a central goal in ecology. However, defining the network structure in a microbial community is very challenging due to their extremely high diversity and as-yet uncultivated status. Although recent advance of metagenomic technologies, such as high throughout sequencing and functional gene arrays, provide revolutionary tools for analyzing microbial community structure, it is still difficult to examine network interactions in a microbial community based on high-throughput metagenomics data.

Results

Here, we describe a novel mathematical and bioinformatics framework to construct ecological association networks named molecular ecological networks (MENs) through Random Matrix Theory (RMT)-based methods. Compared to other network construction methods, this approach is remarkable in that the network is automatically defined and robust to noise, thus providing excellent solutions to several common issues associated with high-throughput metagenomics data. We applied it to determine the network structure of microbial communities subjected to long-term experimental warming based on pyrosequencing data of 16?S rRNA genes. We showed that the constructed MENs under both warming and unwarming conditions exhibited topological features of scale free, small world and modularity, which were consistent with previously described molecular ecological networks. Eigengene analysis indicated that the eigengenes represented the module profiles relatively well. In consistency with many other studies, several major environmental traits including temperature and soil pH were found to be important in determining network interactions in the microbial communities examined. To facilitate its application by the scientific community, all these methods and statistical tools have been integrated into a comprehensive Molecular Ecological Network Analysis Pipeline (MENAP), which is open-accessible now (http://ieg2.ou.edu/MENA).

Conclusions

The RMT-based molecular ecological network analysis provides powerful tools to elucidate network interactions in microbial communities and their responses to environmental changes, which are fundamentally important for research in microbial ecology and environmental microbiology.     

Trends in the search for bioactive microbial metabolites

Summary Bioactive microbial metabolites are attracting increasing attention as useful agents for medicine, veterinary medicine, agriculture, and as unique biochemical tools. A review of the current trends in the discovery-of new metabolites shows that the number of active compounds with non-antibiotic type of activity has increased, resulting in an expansion of the variety of bioactivity of microbial metabolites. Factors that contribute to the increased rate of discovery include: development of new methods for activity measurement, exploitation of novel groups of microorganisms as sources of active compounds, new directions for chemical modification, and incorporation of newer knowledge of biotechnology into screening systems. To exemplify this, typical screening methods, and chemical and biological properties of several bioactive compounds obtained by these methods are discussed.     

An Integrated Approach to Crop Genetic Improvement

The balance between the supply and demand of the major food crops is fragile,fueling concerns for long-term global food security.The rising population,increasing wealth and a proliferation of nonfood uses(e.g.bioenergy) has led to growing demands on agriculture,while increased production is limited by greater urbanization,and the degradation of land.Furthermore,global climate change with increasing temperatures and lower,more erratic rainfall is projected to decrease agricultural yields.There is a predicted need to increase food production by at least 70% by 2050 and therefore an urgent need to develop novel and integrated approaches,incorporating high-throughput phenotyping that will both increaseproduction per unit area and simultaneously improve the resource use efficiency of crops.Yield potential,yield stability,nutrient and water use are all complex multigenic traits and while there is genetic variability,their complexity makes such traits difficult to breed for directly.Nevertheless molecular plant breeding has the potential to deliver substantial improvements,once the component traits and the genes underlying these traits have been identified.In addition,interactions between the individual traits must also be taken into account,a demand that is difficult to fulfill with traditional screening approaches.Identified traits will be incorporated into new cultivars using conventional or biotechnological tools.In order to better understand the relationship between genotype,component traits,and environment over time,a multidisciplinary approach must be adopted to both understand the underlying processes and identify candidate genes,QTLs and traits that can be used to develop improved crops.     

Indirect interactions in the microbial world: specificities and similarities to plant–insect systems

Trophic interactions between bacteria, viruses, and protozoan predators play crucial roles in structuring aquatic microbial communities and regulating microbe-mediated ecosystem functions (biogeochemical processes). In this microbial food web, protozoan predators and viruses share bacteria as a common resource, and protozoan predators can kill viruses [intraguild predation (IGP)] and vice versa, even though these latter processes are probably of less importance. However, protozoan predators (IG predator) and viruses (IG prey) generally occur together in various environments, and this cannot be fully explained by the classic IGP models. In addition, controlled experiments have often demonstrated that protozoan predators have apparently positive effects on viral activity. These surprising patterns can be explained by indirect interactions between them via induced trait changes in bacterial assemblages, which can be compared with trait-mediated indirect interactions (TMIIs) in terrestrial plant–insect systems. Here, we review some trait changes in bacterial assemblages that may positively affect the activities and abundance of viruses. It has been suggested that in bacterial assemblages, protozoan predation may enhance growth conditions for individual bacteria and induce both phenotypic trait changes at the individual (e.g., filament-forming bacteria) and group level as a result of changes in bacterial community composition (e.g., species dominance). We discuss the specificities of aquatic microbial systems and attempt find functional similarities between aquatic microbial systems and terrestrial plant–insect systems with regard to TMII function.     

Rhizosphere microbiome: revisiting the synergy of plant-microbe interactions

Sustainable enhancement in food production from less available arable land must encompass a balanced use of inorganic, organic, and biofertilizer sources of plant nutrients to augment and maintain soil fertility and productivity. The varied responses of microbial inoculants across fields and crops, however, have formed a major bottleneck that hinders its widespread adoption. This necessitates an intricate analysis of the inter-relationships between soil microbial communities and their impact on host plant productivity. The concept of “biased rhizosphere,” which evolved from the interactions among different components of the rhizosphere including plant roots and soil microflora, strives to garner a better understanding of the complex rhizospheric intercommunications. Moreover, knowledge on rhizosphere microbiome is essential for developing strategies for shaping the rhizosphere to benefit the plants. With the advent of molecular and “omics” tools, a better understanding of the plant-microbe association could be acquired which could play a crucial role in drafting the future “biofertilizers.” The present review, therefore aims to (a) to introduce the concepts of rhizosphere hotspots and microbiomes and (b) to detail out the methodologies for creating biased rhizospheres for plant-mediated selection of beneficial microorganisms and their roles in improving plant performance.

     

The art of strain improvement of industrial lactic acid bacteria without the use of recombinant DNA technology

The food industry is constantly striving to develop new products to fulfil the ever changing demands of consumers and the strict requirements of regulatory agencies. For foods based on microbial fermentation, this pushes the boundaries of microbial performance and requires the constant development of new starter cultures with novel properties. Since the use of ingredients in the food industry is tightly regulated and under close scrutiny by consumers, the use of recombinant DNA technology to improve microbial performance is currently not an option. As a result, the focus for improving strains for microbial fermentation is on classical strain improvement methods. Here we review the use of these techniques to improve the functionality of lactic acid bacteria starter cultures for application in industrial-scale food production. Methods will be described for improving the bacteriophage resistance of specific strains, improving their texture forming ability, increasing their tolerance to stress and modulating both the amount and identity of acids produced during fermentation. In addition, approaches to eliminating undesirable properties will be described. Techniques include random mutagenesis, directed evolution and dominant selection schemes.     

Microbial diversity and function in soil: from genes to ecosystems

Soils sustain an immense diversity of microbes, which, to a large extent, remains unexplored. A range of novel methods, most of which are based on rRNA and rDNA analyses, have uncovered part of the soil microbial diversity. The next step in the era of microbial ecology is to extract genomic, evolutionary and functional information from bacterial artificial chromosome libraries of the soil community genomes (the metagenome). Sophisticated analyses that apply molecular phylogenetics, DNA microarrays, functional genomics and in situ activity measurements will provide huge amounts of new data, potentially increasing our understanding of the structure and function of soil microbial ecosystems, and the interactions that occur within them. This review summarizes the recent progress in studies of soil microbial communities with focus on novel methods and approaches that provide new insight into the relationship between phylogenetic and functional diversity.     

Production of natural value-added compounds: an insight into the eugenol biotransformation pathway

During the past few years, the production of natural value-added compounds from microbial sources has gained tremendous importance. Due to an increase in consumer demand for natural products, various food and pharmaceutical industries are continuously in search of novel metabolites obtained from microbial biotransformation. The exploitation of microbial biosynthetic pathways is both feasible and cost effective in the production of natural compounds. The environmentally compatible nature of these products is one major reason for their increasing demand. Novel approaches for natural product biogeneration will take advantage of the current studies on biotechnology, biochemical pathways and microbiology. The interest of the scientific community has shifted toward the use of microbial bioconversion for the production of valuable compounds from natural substrates. The present review focuses on eugenol biotransformation by microorganisms resulting in the formation of various value-added products such as ferulic acid, coniferyl alcohol, vanillin and vanillic acid.     

Metagenomics of microbial and viral life in terrestrial geothermal environments

Geothermally heated regions of Earth, such as terrestrial volcanic areas (fumaroles, hot springs, and geysers) and deep-sea hydrothermal vents, represent a variety of different environments populated by extremophilic archaeal and bacterial microorganisms. Since most of these microbes thriving in such harsh biotopes, they are often recalcitrant to cultivation; therefore, ecological, physiological and phylogenetic studies of these microbial populations have been hampered for a long time. More recently, culture-independent methodologies coupled with the fast development of next generation sequencing technologies as well as with the continuous advances in computational biology, have allowed the production of large amounts of metagenomic data. Specifically, these approaches have assessed the phylogenetic composition and functional potential of microbial consortia thriving within these habitats, shedding light on how extreme physico-chemical conditions and biological interactions have shaped such microbial communities. Metagenomics allowed to better understand that the exposure to an extreme range of selective pressures in such severe environments, accounts for genomic flexibility and metabolic versatility of microbial and viral communities, and makes extreme- and hyper-thermophiles suitable for bioprospecting purposes, representing an interesting source for novel thermostable proteins that can be potentially used in several industrial processes.     

The world within: Quantifying the determinants and outcomes of a host's microbiome

The fungal, bacterial, and viral microbial communities embedded as endosymbionts within all free-living organisms are extremely diverse and encode the vast majority of genes in the biosphere. Microbes in a human, for example, account for 100 times more genes than their host; similar results are emerging for virtually all free-living organisms. Disease is the best studied host–microbe interaction, but endosymbiotic microbial populations and communities also are responsible for critical functions in their hosts including nutrient uptake (plants), reduction in inflammatory responses (animals), digestion (animals), anti-herbivore defenses (plants), and pathogen resistance. In spite of the tremendous diversity and functional importance of the microbial biome to free-living organisms, we have little predictive understanding of the biotic and abiotic factors controlling within-host microbial community composition or the spatial scales at which anthropogenic changes affect host and microbial community interactions and functions. Current research suggests that anthropogenic changes to nutrient supply and food web composition can affect biological systems at scales ranging from individuals to continents. However, while current studies are clarifying the effects of some of these drivers on the structure and functioning of ecosystems, we have far less knowledge of their effects on microbial communities residing within hosts. Given the accelerating progress in metagenome studies, we are poised to make rapid advances in understanding the determinants and effects of within-host microbial communities.     

Metaproteogenomic analysis of a community of sponge symbionts

Sponges harbour complex communities of diverse microorganisms, which have been postulated to form intimate symbiotic relationships with their host. Here we unravel some of these interactions by characterising the functional features of the microbial community of the sponge Cymbastela concentrica through a combined metagenomic and metaproteomic approach. We discover the expression of specific transport functions for typical sponge metabolites (for example, halogenated aromatics, dipeptides), which indicates metabolic interactions between the community and the host. We also uncover the simultaneous performance of aerobic nitrification and anaerobic denitrification, which would aid to remove ammonium secreted by the sponge. Our analysis also highlights the requirement for the microbial community to respond to variable environmental conditions and hence express an array of stress protection proteins. Molecular interactions between symbionts and their host might also be mediated by a set of expressed eukaryotic-like proteins and cell–cell mediators. Finally, some sponge-associated bacteria (for example, a Phyllobacteriaceae phylotype) appear to undergo an evolutionary adaptation process to the sponge environment as evidenced by active mobile genetic elements. Our data clearly show that a combined metaproteogenomic approach can provide novel information on the activities, physiology and interactions of sponge-associated microbial communities.     

Realities and hopes in the application of microbial tools in agriculture

The use of microbial tools to sustainably increase agricultural production has received significant attention from researchers, industries and policymakers. Over the past decade, the market access and development of microbial products have been accelerated by (i) the recent advances in plant-associated microbiome science, (ii) the pressure from consumers and policymakers for increasing crop productivity and reducing the use of agrochemicals, (iii) the rising threats of biotic and abiotic stresses, (iv) the loss of efficacy of some agrochemicals and plant breeding programs and (v) the calls for agriculture to contribute towards mitigating climate change. Although the sector is still in its infancy, the path towards effective microbial products is taking shape and the global market of these products has increased faster than that of agrochemicals. Promising results from using microbes either as biofertilizers or biopesticides have been continually reported, fuelling optimism and high expectations for the sector. However, some limitations, often related to low efficacy and inconsistent performance in field conditions, urgently need to be addressed to promote a wider use of microbial tools. We propose that advances in in situ microbiome manipulation approaches, such as the use of products containing synthetic microbial communities and novel prebiotics, have great potential to overcome some of these current constraints. Much more progress is expected in the development of microbial inoculants as areas such as synthetic biology and nano-biotechnology advance. If key technical, translational and regulatory issues are addressed, microbial tools will not only play an important role in sustainably boosting agricultural production over the next few decades but also contribute towards other sustainable development goals, including job creation and mitigation of the impacts of climate change.     

Metagenomic annotation networks: construction and applications

The derivation and comparison of biological interaction networks are vital for understanding the functional capacity and hierarchical organization of integrated microbial communities. In the current work we present metagenomic annotation networks as a novel taxonomy-free approach for understanding the functional architecture of metagenomes. Specifically, metagenomic operon predictions are exploited to derive functional interactions that are translated and categorized according to their associated functional annotations. The result is a collection of discrete networks of weighted annotation linkages. These networks are subsequently examined for the occurrence of annotation modules that portray the functional and organizational characteristics of various microbial communities. A variety of network perspectives and annotation categories are applied to recover a diverse range of modules with different degrees of annotative cohesiveness. Applications to biocatalyst discovery and human health issues are discussed, as well as the limitations of the current implementation.