Abstract
In symbiotic associations, there is a constant molecular complexity that allows establishment and maintenance of the relationship. Metabolomic profiles have enabled researchers to explain symbiotic associations in terms of their underlying molecules and interactions between the symbiotic partners. In this review, we have selected studies on symbioses as examples that have helped to explain the metabolic integration of bacterial symbionts and their hosts in an effort to understand the molecular fingerprint of animal-microbial symbioses.
Keywords
- symbiosis
- mutualism
- metabolomics
- co-clustering analysis
1. Introduction
The intimate association between two organisms is a very complex biological phenomenon; nevertheless, it is a very common way of life for every living organism on Earth. Symbiotic associations with one or many phylogenetically different organisms provide a fascinating view into how symbionts adapt and co-evolve. As Chaston and Douglas beautifully described in their comprehensive review [1], the omics revolution has transformed our ability to understand symbiotic associations at the molecular level. Researchers have adopted multiple techniques with great fervor in an effort to decipher the basis and complexity of symbiotic associations. Until recent years, the molecular pathways of symbiotic associations could only be studied in the context of genetic changes (transcriptomic studies) and protein profiles (proteomics); however, it is very likely that the establishment of a mutualistic association involved multiple evolutionary changes in the biochemistry and metabolic network of all the partners involved in the symbiosis [1]. Omics biology brings challenges and opportunities; one of the recent advances is the ability to construct a molecular metabolic catalog of an organism within a symbiotic association. Metabolomics refers to the analytical approach used to study different cell products (“chemical fingerprints”) that help to understand the physiological state of an organism [2].
In this section, we provide a comprehensive description of four experiments where the approach of metabolomics was selected in a particular type of animal-microbial symbiosis, in order to answer specific questions in symbiosis research.
2. Exemplars of metabolomic approaches in symbiosis research
2.1. Inferring metabolic interactions in arbuscular mycorrhizal symbiosis
Our exemplar of metabolomics studies of microbe-plant interactions is a set of observations by Schweiger et al. [3] that describe species-specific leaf metabolic responses to arbuscular mycorrhiza (AM) [4]. Arbuscular mycorrhiza is a unique symbiotic association between root arbuscular mycorrhizal fungi (AMF) and plants [4]. This is an ancient and widespread association where the fungus improves water uptake to the host plant, and in return the fungus receives plant carbohydrates. The fungus is restricted to the roots of the plant; however, the biochemical pathways and the involvement of exchanged substances are reflected on systemic root tissues affecting the chemical composition of plant tissues (defined as “phytometabolome”) [4].
Comparative studies conducted on five different plant-AMF associations demonstrate that foliar metabolome is highly plant-species-specific, with low degrees of conservation across species. The experimental design was crucial to the success of this analysis, with the metabolome analysis performed on leaves of five plant species exposed to the worldwide distributed AMF
2.2. Metabolomic profile of the ryegrass-endophyte symbiosis
Along the lines of microbe-plant interactions, there is an interesting study conducted by Cao et al. [5] that is of particular relevance for symbiosis research. The metabolomics profile of perennial ryegrass (
Twenty-four perennial ryegrass samples comprising three tissue types (immature leaves, blades, and mature leaves) were examined of both endophyte-infected plants and endophyte free as a control. Targeted metabolomics analysis was used as the quantitative approach that provided identities of 70 metabolites based on the available databases of reference compounds. The use of targeted metabolomics in combination with microarray data provided better identification and classification Accuracy of compounds, as well as greater insights into the dynamics and fluxes of the newly identified metabolites. Results of this comprehensive study included the identification of accumulated alkaloids in the mature tissues of endophyte-infected ryegrass, and the co-clustering analysis of microarray data-identified genes with distinctive expression patterns which coincide with the pattern of alkaloid accumulation [5]. Figure 2 summarizes the findings of this study. Results of this study indicate that co-clustering analysis is not a straightforward task no matter what kind of algorithm is used, and that the integration of transcriptomics and metabolomics can generate noisy data. However, this study demonstrated that co-cluster analysis could be a comprehensive choice to gain a more complete understanding of a complex biological system involving two entirely different taxa that are intertwined in their metabolic capabilities.
2.3. Metabolomic profile of symbiotic protection against pathogens
It is believed that specific strains from the gut microbiota can influence host immunity and protect from infection by pathogenic bacteria. One example is the early and prevalent gut colonizer
One study conducted by Fukuda et al. [7] used a combined “omics” strategy in an effort to gain a better understanding of the protective effect of
Results from this study indicate that mice bearing the strain
2.4. Metabolomics of a beneficial marine bacterium
The marine luminescent bacterium
In a recent study conducted by Chavez-Dozal et al. [8], both proteomic and metabolomic profiles were performed in parallel in strains of
Biofilms are a complex microbial community composed of cells encased within a self-produced exopolymeric matrix. Expression profiles of biofilm communities reveal the composition of the matrix, which include a combination of lipids, polysaccharides, proteins, and DNA [9, 10].
Results of this study revealed a time-resolved picture of approximately 100 proteins and 200 metabolites present in the biofilm state of
3. Concluding remarks
Metabolomic approaches are increasingly selected for multiple purposes of symbiosis research. Although other “omic” approaches are needed to understand molecular function in symbiotic associations, the emerging use of metabolomics provides a new level of biochemical sophistication. The different examples provided in this mini review are only some of the pillar studies that included the use of either metabolomics or a combinational analysis of metabolomics with transcriptomics/proteomics of different mutualistic systems; however, many more studies are in progress using metabolomics profiles to define and characterize molecular and biochemical pathways that are important for establishment and persistence of symbiotic associations. The advancement of technologies that allows higher resolution of minute concentrations of proteins and their modulation will expand the area of metabolomics research and will enable a better perspective of the physiological state of organisms as single entities (otherwise known as the holobiome).
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