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

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.

Mixed cultures as model communities: hunting for ubiquitous microorganisms, their partners, and interactions

“…These results showed that bacteria could use nanotubes to exchange nutrients among connected cells and thus help to distribute metabolic functions within microbial communities (Pande et al 2015). Mixed cultures are also highly relevant for drug research, because they allow identification of biologically active compounds (Netzker et al 2015). This principle is nicely illustrated in a study in which the model fungus Aspergillus nidulans was co-cultivated with a collection of 58 soil-dwelling Actinobacteria (Schroeckh et al 2009).…”

<i>Aspergillus flavus</i> Secondary Metabolites: More than Just Aflatoxins

“…Several methods have been used to activate silent SM gene clusters in fungi and these have been summarized in a number of excellent reviews 21,[105][106][107] . These include over-expression of global or pathway-specific transcriptional regulators, expression of SM cluster genes in heterologous hosts, co-culture of a fungal strain with another micro-organism, proteomics, exposure to epigenetic modifiers and antibiotics and alteration of media composition.…”

Computational Analysis Reveals Industrial Natural Products and Toxins in Charcoal Rot Pathogen, <i>Macrophomina phaseolina</i>

“…Therefore, in order to initiate the activation of silent fungal secondary metabolite gene clusters, a number of strategies are developed (use of inducer, co-cultivation with bacteria, epigenetic re-modelling, use of rare earth elements, ribosomal engineering and others) [46][47][48] . Further experimental strategies may be applied to these existing strategies to validate if these aforementioned PKS are responsible for producing these potentially important natural products.…”