Fungi Treated with Small Chemicals Exhibit Increased Antimicrobial Activity against Facultative Bacterial and Yeast Pathogens

Abstract

For decades, fungi have been the main source for the discovery of novel antimicrobial drugs. Recent sequencing efforts revealed a still high number of so far unknown “cryptic” secondary metabolites. The production of these metabolites is presumably epigenetically silenced under standard laboratory conditions. In this study, we investigated the effect of six small mass chemicals, of which some are known to act as epigenetic modulators, on the production of antimicrobial compounds in 54 spore forming fungi. The antimicrobial effect of fungal samples was tested against clinically facultative pathogens and multiresistant clinical isolates. In total, 30 samples of treated fungi belonging to six different genera reduced significantly growth of different test organisms compared to the untreated fungal sample (growth log reduction 0.3–4.3). For instance, the pellet of Penicillium restrictum grown in the presence of butyrate revealed significant higher antimicrobial activity against Staphylococcus (S.) aureus and multiresistant S. aureus strains and displayed no cytotoxicity against human cells, thus making it an ideal candidate for antimicrobial compound discovery. Our study shows that every presumable fungus, even well described fungi, has the potential to produce novel antimicrobial compounds and that our approach is capable of rapidly filling the pipeline for yet undiscovered antimicrobial substances.

The Anticandidal and Toxicity Properties of Lampranthus francisci

“…DMSO is a polar solvent that has the ability to dissolve a wide range of compounds and is miscible with most solvents [45]. Zutz et al [46] found that DMSO up to a concentration of 2.5% did not alter the growth of C. albicans. In this study, DMSO was used at a final concentration of 3% and it was noted it had a growth stimulatory effect at all tested concentrations on C. krusei only.…”

Valproic Acid Induces Antimicrobial Compound Production in Doratomyces microspores

“…The antimicrobial activity testing was performed as previously described ( Zutz et al, 2014 ). Additionally to the indicator organisms S. aureus, Candida ( C. ) albicans and Pseudomonas ( P. ) aeruginosa we used also Klebsiella ( K. ) pneumoniae, Staphylococcus ( S .)…”

“…In a previous work we have established a screening system based on the use of such low molecular weight molecules, like VPA, to induce the production of “cryptic” antimicrobial compounds in fungi ( Zutz et al, 2014 ). In this work we focused on one hit candidate, the fungus D .…”

From Axenic to Mixed Cultures: Technological Advances Accelerating a Paradigm Shift in Microbiology

“…activation of epigenetic factors) [35,36]. Whereas the former require a priori knowledge of a specific BGC [37][38][39], the latter are less-specific and modify global gene expression with direct and indirect consequences on the expression of multiple BGCs [40][41][42][43][44][45][46][47]. Further pleiotropic approaches rely on variations of the growth media (e.g.…”

“…Further general approaches for "genome mining" rely on epigenetic factors involved in chromatin remodeling or global gene expression, either by using mutants or by adding exogenously chemical elicitors like valproic acid, 5-azacytidine or suberoylanilide hydroxamic acid [41][42][43][45][46][47]145,146]; on the exogenous addition of chemicals like GlcNAc, cAMP, FA synthesis inhibitors, antibiotics or quorum sensing molecules [29,81,139,140,147,148], rare earth elements like scandium [149];…”