1. Hubertus Haas  Is a corresponding author
  1. Medical University of Innsbruck, Austria

Fungi affect our lives in many different ways, both positive and negative. One of the reasons for this is that most fungi produce a multitude of small organic molecules called secondary metabolites. Different species employ a strikingly diverse arsenal of secondary metabolites, most of which are released into the environment (Sanchez et al., 2012). Secondary metabolites are not directly required to ensure the growth of the organism, but confer an advantage under specific environmental conditions.

Fungi use secondary metabolites to defend against predators and competitors, for chemical communication, or in the case of pathogenic fungi, to manipulate their animal and plant hosts (Brakhage et al., 2013). Secondary metabolism is therefore likely to be shaped to a large extent by interactions with other organisms. For example, fungi secrete enzymes to digest their food, which allows them to grow on virtually any organic matter, but also means that the products of their digestion are in principle a free meal for other organisms. And by secreting secondary metabolites that target these organisms, fungi are able to defend their niche to avoid competitors taking advantage of the available food.

Well-known examples of secondary metabolites produced by fungi are the poisonous food contaminant aflatoxin, the antibiotic penicillin and the anticancer drug taxol. These molecules illustrate the negative and positive effects of secondary metabolites on humans, and underline their outstanding potential for medicinal use. However, it is not known what roles most of these molecules play in the lives of the fungi that produce them. Moreover, most secondary metabolites are not produced when the fungi are grown in the laboratory, which makes it difficult to characterize them. Now in eLife, Matthias Brock and co-workers – including Markus Gressler as first author – report a new role for a major secondary metabolite called terrein, and characterize the environmental stimuli that induce the mold Aspergillus terreus to produce it (Figure 1; Gressler et al., 2015).

Environmental signals activate production of terrein by the mold Aspergillus terreus to improve its competitiveness.

To adapt to changing environmental conditions and different ecological niches, microorganisms need to be able to sense and respond to environmental signals. Gressler et al. identified three independent signals that stimulate production of the compound terrein by Aspergillus terreus – nitrogen starvation, methionine, and iron starvation. In this mold's natural niche within plants and in the soil surrounding plant roots, terrein is a chemical weapon used to inhibit the growth of bacteria, plants and other fungi, but also helps to improve iron supply to the producer.

A. terreus is a common soil-borne fungus that feeds on dead organic material, but is also able to invade plants and cause life-threatening infections in humans with weakened immune systems. Genome analysis indicated that this fungus might produce more than 68 secondary metabolites, although only 14—including the cholesterol-lowering drug lovastatin—have been identified so far (Guo and Wang, 2014). The compound terrein was first described 80 years ago, but how A. terreus makes terrein was only resolved in 2014 by the Brock group (Zaehle et al., 2014). Terrein was previously shown to be harmful to plant cells as it inhibits the germination of seeds and causes lesions on plant surfaces, and probably helps the fungus to colonize its host.

Based on the observation that potato extract (an ingredient of a standard medium used for culturing fungi) activates the production of terrein, Gressler et al. – who are based at the Hans Knoell Institute, Friedrich Schiller University and Nottingham University – systematically characterized how different conditions impact terrein production. This analysis revealed that the genes that encode the terrein biosynthetic pathway are activated by three independent environmental stimuli: nitrogen starvation, iron starvation, and the presence of the amino acid methionine. These conditions are typically found in the plant and the plant root area, known as the rhizosphere, and are used by the mold to sense these niches.

Next, by genetic engineering of the mold, Gressler et al. identified three transcription factors that activate genes in response to environmental signals. Previous studies have revealed the roles of these regulators in altering the production of primary metabolites – which are required for normal growth and reproduction – in response to stress and the availability of nitrogen and iron (Haas, 2012; Tudzynski, 2014). However, it is not known how the mold perceives the methionine signal. Nitrogen and iron also regulate the production of other secondary metabolites (Tudzynski, 2014; Wiemann et al., 2014), suggesting that these environmental cues are often used to adjust secondary metabolism. The complex environmental control of terrein production revealed by Gressler et al. represents a prime example of how microorganisms adapt their secondary metabolism to the niche they inhabit.

In addition to its ability to inhibit the growth of plants, it has been reported that terrein can inhibit the growth of bacteria, fungi and mammalian cells, and that it can also act as an antioxidant and anti-inflammatory (Zaehle et al., 2014). Now, Gressler et al. have discovered that terrein supports iron uptake by the fungus that produces it, but inhibits the growth of even closely related molds. This clearly indicates that terrein improves the competiveness of the producer. It will be exciting to learn how terrein is able to influence many different biological processes in different organisms, and how the producer protects itself against this molecule.

References

Article and author information

Author details

  1. Hubertus Haas

    Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    For correspondence
    hubertus.haas@i-med.ac.at
    Competing interests
    The author declares that no competing interests exist.

Publication history

  1. Version of Record published: September 1, 2015 (version 1)

Copyright

© 2015, Haas

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,714
    Page views
  • 205
    Downloads
  • 3
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Hubertus Haas
(2015)
Microbial Ecology: How to trigger a fungal weapon
eLife 4:e10504.
https://doi.org/10.7554/eLife.10504

Further reading

    1. Biochemistry and Chemical Biology
    2. Epidemiology and Global Health
    Lang Pan et al.
    Research Article

    Background:

    Few studies have assessed the role of individual plasma cholesterol levels in the association between egg consumption and the risk of cardiovascular diseases. This research aims to simultaneously explore the associations of self-reported egg consumption with plasma metabolic markers and these markers with the risk of cardiovascular disease (CVD).

    Methods:

    Totally 4778 participants (3401 CVD cases subdivided into subtypes and 1377 controls) aged 30–79 were selected based on the China Kadoorie Biobank. Targeted nuclear magnetic resonance was used to quantify 225 metabolites in baseline plasma samples. Linear regression was conducted to assess associations between self-reported egg consumption and metabolic markers, which were further compared with associations between metabolic markers and CVD risk.

    Results:

    Egg consumption was associated with 24 out of 225 markers, including positive associations for apolipoprotein A1, acetate, mean HDL diameter, and lipid profiles of very large and large HDL, and inverse associations for total cholesterol and cholesterol esters in small VLDL. Among these 24 markers, 14 were associated with CVD risk. In general, the associations of egg consumption with metabolic markers and of these markers with CVD risk showed opposite patterns.

    Conclusions:

    In the Chinese population, egg consumption is associated with several metabolic markers, which may partially explain the protective effect of moderate egg consumption on CVD.

    Funding:

    This work was supported by the National Natural Science Foundation of China (81973125, 81941018, 91846303, 91843302). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 81390541, 81390544), and Chinese Ministry of Science and Technology (2011BAI09B01). The funders had no role in the study design, data collection, data analysis and interpretation, writing of the report, or the decision to submit the article for publication.

    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics
    Atefeh Rafiei et al.
    Research Article Updated

    Doublecortin (DCX) is a microtubule (MT)-associated protein that regulates MT structure and function during neuronal development and mutations in DCX lead to a spectrum of neurological disorders. The structural properties of MT-bound DCX that explain these disorders are incompletely determined. Here, we describe the molecular architecture of the DCX–MT complex through an integrative modeling approach that combines data from X-ray crystallography, cryo-electron microscopy, and a high-fidelity chemical crosslinking method. We demonstrate that DCX interacts with MTs through its N-terminal domain and induces a lattice-dependent self-association involving the C-terminal structured domain and its disordered tail, in a conformation that favors an open, domain-swapped state. The networked state can accommodate multiple different attachment points on the MT lattice, all of which orient the C-terminal tails away from the lattice. As numerous disease mutations cluster in the C-terminus, and regulatory phosphorylations cluster in its tail, our study shows that lattice-driven self-assembly is an important property of DCX.