Valproic acid induces antimicrobial compound production in Doratomyces microspores.
One of the biggest challenges in public health is the rising number of antibiotic resistant pathogens and the lack of novel antibiotics. In recent years there is a rising focus on fungi as sources of antimicrobial compounds due to their ability to produce a large variety of bioactive compounds and t...
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doaj-f47a24f277cd48168c8395ae2f79d6fa2020-11-24T22:23:45ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-04-01710.3389/fmicb.2016.00510190041Valproic acid induces antimicrobial compound production in Doratomyces microspores.Christoph eZutz0Christoph eZutz1Markus eBacher2Alexandra eParich3Bernhard eKluger4Agnieszka eGacek-Matthews5Agnieszka eGacek-Matthews6Rainer eSchuhmacher7Martin eWagner8Kathrin eRychli9Joseph eStrauss10Joseph eStrauss11Joseph eStrauss12University of Veterinary Medicine ViennaResearch Platform Bioactive Microbial Metabolites -BiMMUniversity of Natural Resources and Life Science, Vienna (BOKU)University of Natural Resources and Life Science, Vienna (BOKU)University of Natural Resources and Life Science, Vienna (BOKU)University of Natural Resources and Life Science, Vienna (BOKU)University of Veterinary Medicine ViennaUniversity of Natural Resources and Life Science, Vienna (BOKU)University of Veterinary Medicine ViennaUniversity of Veterinary Medicine ViennaUniversity of Natural Resources and Life Science, Vienna (BOKU)Research Platform Bioactive Microbial Metabolites -BiMMAIT-Austrian Institute of TechnologyOne of the biggest challenges in public health is the rising number of antibiotic resistant pathogens and the lack of novel antibiotics. In recent years there is a rising focus on fungi as sources of antimicrobial compounds due to their ability to produce a large variety of bioactive compounds and the observation that virtually every fungus may still contain yet unknown so called cryptic, often silenced, compounds. These putative metabolites could include novel bioactive compounds. Considerable effort is spent on methods to induce production of these cryptic metabolites. One approach is the use of small molecule effectors, potentially influencing chromatin landscape in fungi. We observed that the supernatant of the fungus Doratomyces (D.) microsporus treated with valproic acid (VPA) displayed antimicrobial activity against Staphylococcus (S.) aureus and two methicillin resistant clinical S. aureus isolates. VPA treatment resulted in enhanced production of seven antimicrobial compounds: cyclo-(L-proline-L-methionine) (cPM), p-hydroxybenzaldehyde, cyclo-(phenylalanine-proline) (cFP), indole-3-carboxylic acid, phenylacetic acid (PAA) and indole-3-acetic acid. The production of the antimicrobial compound phenyllactic acid was exclusively detectable after VPA treatment. Furthermore three compounds, cPM, cFP and PAA, were able to boost the antimicrobial activity of other antimicrobial compounds. cPM, for the first time isolated from fungi, and to a lesser extent PAA, are even able to decrease the minimal inhibitory concentration of ampicillin in MRSA strains. In conclusion we could show in this study that VPA treatment is a potent tool for induction of cryptic antimicrobial compound production in fungi, and that the induced compounds are not exclusively linked to the secondary metabolism. Furthermore this is the first discovery of the rare diketopiperazine cPM in fungi. Additionally we could demonstrate that cPM and PAA boost antibiotic activity against antibiotic resistant strains, suggesting a possible application in combinatorial antibiotic treatment against resistant pathogens.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00510/fullFungiValproic Acidantimicrobial compoundsDiketopiperazineDoratomyces |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christoph eZutz Christoph eZutz Markus eBacher Alexandra eParich Bernhard eKluger Agnieszka eGacek-Matthews Agnieszka eGacek-Matthews Rainer eSchuhmacher Martin eWagner Kathrin eRychli Joseph eStrauss Joseph eStrauss Joseph eStrauss |
spellingShingle |
Christoph eZutz Christoph eZutz Markus eBacher Alexandra eParich Bernhard eKluger Agnieszka eGacek-Matthews Agnieszka eGacek-Matthews Rainer eSchuhmacher Martin eWagner Kathrin eRychli Joseph eStrauss Joseph eStrauss Joseph eStrauss Valproic acid induces antimicrobial compound production in Doratomyces microspores. Frontiers in Microbiology Fungi Valproic Acid antimicrobial compounds Diketopiperazine Doratomyces |
author_facet |
Christoph eZutz Christoph eZutz Markus eBacher Alexandra eParich Bernhard eKluger Agnieszka eGacek-Matthews Agnieszka eGacek-Matthews Rainer eSchuhmacher Martin eWagner Kathrin eRychli Joseph eStrauss Joseph eStrauss Joseph eStrauss |
author_sort |
Christoph eZutz |
title |
Valproic acid induces antimicrobial compound production in Doratomyces microspores. |
title_short |
Valproic acid induces antimicrobial compound production in Doratomyces microspores. |
title_full |
Valproic acid induces antimicrobial compound production in Doratomyces microspores. |
title_fullStr |
Valproic acid induces antimicrobial compound production in Doratomyces microspores. |
title_full_unstemmed |
Valproic acid induces antimicrobial compound production in Doratomyces microspores. |
title_sort |
valproic acid induces antimicrobial compound production in doratomyces microspores. |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2016-04-01 |
description |
One of the biggest challenges in public health is the rising number of antibiotic resistant pathogens and the lack of novel antibiotics. In recent years there is a rising focus on fungi as sources of antimicrobial compounds due to their ability to produce a large variety of bioactive compounds and the observation that virtually every fungus may still contain yet unknown so called cryptic, often silenced, compounds. These putative metabolites could include novel bioactive compounds. Considerable effort is spent on methods to induce production of these cryptic metabolites. One approach is the use of small molecule effectors, potentially influencing chromatin landscape in fungi. We observed that the supernatant of the fungus Doratomyces (D.) microsporus treated with valproic acid (VPA) displayed antimicrobial activity against Staphylococcus (S.) aureus and two methicillin resistant clinical S. aureus isolates. VPA treatment resulted in enhanced production of seven antimicrobial compounds: cyclo-(L-proline-L-methionine) (cPM), p-hydroxybenzaldehyde, cyclo-(phenylalanine-proline) (cFP), indole-3-carboxylic acid, phenylacetic acid (PAA) and indole-3-acetic acid. The production of the antimicrobial compound phenyllactic acid was exclusively detectable after VPA treatment. Furthermore three compounds, cPM, cFP and PAA, were able to boost the antimicrobial activity of other antimicrobial compounds. cPM, for the first time isolated from fungi, and to a lesser extent PAA, are even able to decrease the minimal inhibitory concentration of ampicillin in MRSA strains. In conclusion we could show in this study that VPA treatment is a potent tool for induction of cryptic antimicrobial compound production in fungi, and that the induced compounds are not exclusively linked to the secondary metabolism. Furthermore this is the first discovery of the rare diketopiperazine cPM in fungi. Additionally we could demonstrate that cPM and PAA boost antibiotic activity against antibiotic resistant strains, suggesting a possible application in combinatorial antibiotic treatment against resistant pathogens. |
topic |
Fungi Valproic Acid antimicrobial compounds Diketopiperazine Doratomyces |
url |
http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00510/full |
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