Limits...
Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters.

Netzker T, Fischer J, Weber J, Mattern DJ, König CC, Valiante V, Schroeckh V, Brakhage AA - Front Microbiol (2015)

Bottom Line: The high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms.Recently, it was shown that interspecies "talk" between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel SMs by the involved species.In addition, the role of chromatin remodeling in the induction is examined, and methodical perspectives for the analysis of natural products are presented.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute , Jena, Germany ; Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena , Jena, Germany.

ABSTRACT
Microorganisms form diverse multispecies communities in various ecosystems. The high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms. A key role in this communication is played by secondary metabolites (SMs), which are also called natural products. Recently, it was shown that interspecies "talk" between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel SMs by the involved species. This review focuses on mixed microbial cultivation, mainly between bacteria and fungi, with a special emphasis on the induced formation of fungal SMs in co-cultures. In addition, the role of chromatin remodeling in the induction is examined, and methodical perspectives for the analysis of natural products are presented. As an example for an intermicrobial interaction elucidated at the molecular level, we discuss the specific interaction between the filamentous fungi Aspergillus nidulans and Aspergillus fumigatus with the soil bacterium Streptomyces rapamycinicus, which provides an excellent model system to enlighten molecular concepts behind regulatory mechanisms and will pave the way to a novel avenue of drug discovery through targeted activation of silent SM gene clusters through co-cultivations of microorganisms.

No MeSH data available.


Related in: MedlinePlus

Microorganismic multispecies communities form secondary metabolites that contribute to the stabilization/changes in these companionships. In nature, microorganisms process signals from both abiotic and biotic environments. The latter represent secondary metabolites or natural products whose formation is often suppressed in pure cultures under standard conditions in the laboratory. Microbial mixed cultivation is therefore a suitable means to exploit their potential for natural product discovery and to study the molecular concepts behind the regulatory interactions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4403501&req=5

Figure 1: Microorganismic multispecies communities form secondary metabolites that contribute to the stabilization/changes in these companionships. In nature, microorganisms process signals from both abiotic and biotic environments. The latter represent secondary metabolites or natural products whose formation is often suppressed in pure cultures under standard conditions in the laboratory. Microbial mixed cultivation is therefore a suitable means to exploit their potential for natural product discovery and to study the molecular concepts behind the regulatory interactions.

Mentions: Secondary metabolites (SMs) are low-molecular-mass organic compounds that, unlike primary metabolites, are not directly involved in growth, development or reproduction of the producing organism. Up until 2014 ∼170,000 natural products have been characterized from both marine and terrestrial organisms (Seyedsayamdost and Clardy, 2014; Chapman and Hall, 2015). Microorganisms are able to synthesize a large number of SMs, but the exact number is not known. Furthermore, mining of microbial genomes revealed the presence of numerous SM gene clusters, displaying a discrepancy between the number of putative genes involved in secondary metabolism and the known SMs in a single microbe (Bergmann et al., 2007; Sanchez et al., 2012; Craney et al., 2013). For example, the model fungus Aspergillus nidulans is potentially able to produce 32 polyketides, 14 non-ribosomal peptides and two indole alkaloids (Brakhage et al., 2008; Rank et al., 2010), with little more than 50% of the produced SMs being identified. Furthermore, SMs can be found in diverse environments and even chemical biogeographic distribution maps for biomedically valuable families of natural products in the environment have been created (Charlop-Powers et al., 2014). A number of these compounds have important pharmacological applications and are used as antibiotics/antibacterial drugs (Brakhage, 2013). Unfortunately, antibiotic resistance is spreading faster than the development of new antibiotics. As a consequence, there is the need for a constant provision of new compounds for the antibiotic development pipeline (Bbosa et al., 2014; Nathan and Cars, 2014). This is contrasted with a continuous rise in re-isolation of already known natural products (Strand et al., 2014). To manage this conflict, a more targeted natural product search is necessary. This effort directs SM research incrementally to a deeper understanding of the physiological relevance and ecological significance of SMs. It is generally accepted that in nature a substantial benefit to the SM producers must exist, simply arising from the fact that these very energy consuming biosynthetic pathways were maintained through evolution. An early postulated explanation for the role of SMs in nature was its function to defend the habitats of the producers by inhibiting the growth of its competitors (Davies, 1990; Brakhage et al., 2005; Galán et al., 2013). Another more recent hypothesis postulates an association between epibiotic predation and antibiotic production due to widespread predatory abilities in the genus Streptomyces (Kumbhar et al., 2014). At low, therefore non-inhibitory concentrations, such molecules are believed to function as signaling molecules (Aminov, 2009; Andersson and Hughes, 2014). This is supported by the assumption that over millions of years the evolution of SMs happened because microorganisms used them as chemical signals for communication between cells of the same species, different species (Figure 1) or between host cells, e.g., as endophytes in other microorganisms (Partida-Martinez and Hertweck, 2005) or plants (Brader et al., 2014).


Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters.

Netzker T, Fischer J, Weber J, Mattern DJ, König CC, Valiante V, Schroeckh V, Brakhage AA - Front Microbiol (2015)

Microorganismic multispecies communities form secondary metabolites that contribute to the stabilization/changes in these companionships. In nature, microorganisms process signals from both abiotic and biotic environments. The latter represent secondary metabolites or natural products whose formation is often suppressed in pure cultures under standard conditions in the laboratory. Microbial mixed cultivation is therefore a suitable means to exploit their potential for natural product discovery and to study the molecular concepts behind the regulatory interactions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403501&req=5

Figure 1: Microorganismic multispecies communities form secondary metabolites that contribute to the stabilization/changes in these companionships. In nature, microorganisms process signals from both abiotic and biotic environments. The latter represent secondary metabolites or natural products whose formation is often suppressed in pure cultures under standard conditions in the laboratory. Microbial mixed cultivation is therefore a suitable means to exploit their potential for natural product discovery and to study the molecular concepts behind the regulatory interactions.
Mentions: Secondary metabolites (SMs) are low-molecular-mass organic compounds that, unlike primary metabolites, are not directly involved in growth, development or reproduction of the producing organism. Up until 2014 ∼170,000 natural products have been characterized from both marine and terrestrial organisms (Seyedsayamdost and Clardy, 2014; Chapman and Hall, 2015). Microorganisms are able to synthesize a large number of SMs, but the exact number is not known. Furthermore, mining of microbial genomes revealed the presence of numerous SM gene clusters, displaying a discrepancy between the number of putative genes involved in secondary metabolism and the known SMs in a single microbe (Bergmann et al., 2007; Sanchez et al., 2012; Craney et al., 2013). For example, the model fungus Aspergillus nidulans is potentially able to produce 32 polyketides, 14 non-ribosomal peptides and two indole alkaloids (Brakhage et al., 2008; Rank et al., 2010), with little more than 50% of the produced SMs being identified. Furthermore, SMs can be found in diverse environments and even chemical biogeographic distribution maps for biomedically valuable families of natural products in the environment have been created (Charlop-Powers et al., 2014). A number of these compounds have important pharmacological applications and are used as antibiotics/antibacterial drugs (Brakhage, 2013). Unfortunately, antibiotic resistance is spreading faster than the development of new antibiotics. As a consequence, there is the need for a constant provision of new compounds for the antibiotic development pipeline (Bbosa et al., 2014; Nathan and Cars, 2014). This is contrasted with a continuous rise in re-isolation of already known natural products (Strand et al., 2014). To manage this conflict, a more targeted natural product search is necessary. This effort directs SM research incrementally to a deeper understanding of the physiological relevance and ecological significance of SMs. It is generally accepted that in nature a substantial benefit to the SM producers must exist, simply arising from the fact that these very energy consuming biosynthetic pathways were maintained through evolution. An early postulated explanation for the role of SMs in nature was its function to defend the habitats of the producers by inhibiting the growth of its competitors (Davies, 1990; Brakhage et al., 2005; Galán et al., 2013). Another more recent hypothesis postulates an association between epibiotic predation and antibiotic production due to widespread predatory abilities in the genus Streptomyces (Kumbhar et al., 2014). At low, therefore non-inhibitory concentrations, such molecules are believed to function as signaling molecules (Aminov, 2009; Andersson and Hughes, 2014). This is supported by the assumption that over millions of years the evolution of SMs happened because microorganisms used them as chemical signals for communication between cells of the same species, different species (Figure 1) or between host cells, e.g., as endophytes in other microorganisms (Partida-Martinez and Hertweck, 2005) or plants (Brader et al., 2014).

Bottom Line: The high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms.Recently, it was shown that interspecies "talk" between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel SMs by the involved species.In addition, the role of chromatin remodeling in the induction is examined, and methodical perspectives for the analysis of natural products are presented.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute , Jena, Germany ; Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena , Jena, Germany.

ABSTRACT
Microorganisms form diverse multispecies communities in various ecosystems. The high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms. A key role in this communication is played by secondary metabolites (SMs), which are also called natural products. Recently, it was shown that interspecies "talk" between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel SMs by the involved species. This review focuses on mixed microbial cultivation, mainly between bacteria and fungi, with a special emphasis on the induced formation of fungal SMs in co-cultures. In addition, the role of chromatin remodeling in the induction is examined, and methodical perspectives for the analysis of natural products are presented. As an example for an intermicrobial interaction elucidated at the molecular level, we discuss the specific interaction between the filamentous fungi Aspergillus nidulans and Aspergillus fumigatus with the soil bacterium Streptomyces rapamycinicus, which provides an excellent model system to enlighten molecular concepts behind regulatory mechanisms and will pave the way to a novel avenue of drug discovery through targeted activation of silent SM gene clusters through co-cultivations of microorganisms.

No MeSH data available.


Related in: MedlinePlus