Imaging Mass Spectrometry and Genome Mining Reveal Highly Antifungal Virulence Factor of Mushroom Soft Rot Pathogen

Abstract

Caught in the act: imaging mass spectrometry of a button mushroom infected with the soft rot pathogen Janthinobacterium agaricidamnosum in conjunction with genome mining revealed jagaricin as a highly antifungal virulence factor that is not produced under standard cultivation conditions. The structure of jagaricin was rigorously elucidated by a combination of physicochemical analyses, chemical derivatization, and bioinformatics.

Antibiotics from neglected bacterial sources

“…Jagaricin is a cyclic lipopeptide product of an NRPS, which appears to only be activated when the bacteria are in contact with Agaricus bisporus (common button mushroom) or when grown in complex media. Jagaricin is highly active against human pathogenic fungi including C. albicans, Aspergillus fumigatus and Aspergillus terreus at submicromolar concentrations and is partly responsible for the lesions seen in infected mushrooms (Graupner et al, 2012). Currently, the mode of action of jagaricin is unknown, however, this study shows the value of investigating microbial-fungal interactions to identify natural products targeting specific organisms.…”

“…Antibacterial compounds, such as the janthinocins (O'Sullivan et al, 1990) and the antifungal compounds violacein (Pantanella et al, 2007) and jagaricin (Graupner et al, 2012) (Graupner et al, 2012;Pantanella et al, 2007) have been identified from Janthinobacterium species. Janthinobacterium spp.…”

“…A recent study attempting to identify antifungal compounds by investigating mushroom-pathogenic bacteria has shown that Janthinobacterium agaricidamnosum, a known cause of "soft rot" disease in mushrooms, produces the antifungal compound jagaricin ( Fig. 1) (Graupner et al, 2012). The identification of jagaricin involved studying the infectious process of the bacterium in vivo using mass spectrometry imaging, followed by genome sequencing and mining of the subsequent data to confirm its biosynthetic gene cluster.…”

Strategies for Circumventing Bacterial Resistance Mechanisms

“…The vast realm of the so-called "uncultured" bacteria may open for exploration, as we further understand their chemical means of communication (Nikitushkin et al 2013;Wilson and Piel 2013). Advances in structure analysis (Seger et al 2013;El-Elimat et al 2013), including the ability to directly interrogate the presence of secondary metabolites by imaging mass spectrometry (Watrous et al 2012;Graupner et al 2012), have diminished dereplication as a barrier to discovery. Finally, numerous advances in the understanding of the genomic organization used for secondary metabolite biosynthesis (Andersen et al 2013;Wright 2014), coupled to an understanding of the genetic control of biosynthesis by small molecules (Ahmed et al 2013), by pathway metabolic modeling (Breitling et al 2013), and by development of new bacterial vectors (Ongley et al 2013;Komatsu et al 2013), anticipate a future ability to attain (by manipulation of starting material, enzymes, and vectors) unprecedented antibacterial structure (Baltz 2014;Craney et al 2013;Walsh et al 2013;Zakeri and Lu 2013;Thaker et al 2013;Thaker and Wright 2014).…”

Mass spectrometry of natural products: current, emerging and future technologies

“…MALDI-IMS has been extensively applied for NP analysis, by providing 2D spatial distribution of secondary metabolites from several living organisms 44 . Some of the examples include use of MALDI-IMS to investigate production of antibiotics by symbiotic Streptomyces in the larval cocoon of beewolf digger wasps 45 and by Streptomyces and other actinomycetes in leaf-cutting ants 46, 47 , production of NPs in bacterial co-cultures 48-51 , gut 52 , plants 53 , and marine organisms 54 including cyanobacteria 55 , zoanthids 56 and marine sponges 55, 57-59 .…”