Biology subjects

Stroe, M. C.

Publications and source records attributed to Stroe, M. C..

4 recordsLinked to original sources

bioRxiv2023

Bacteria-induced activation of a fungal silent gene cluster is controlled by histone deacetylase Sirtuin E

Filamentous fungi encode an untapped reservoir of natural products whose biosynthesis enzymes are often encoded by gene clusters. The majority of these gene clusters are only activated under distinct environmental conditions such as the presence of distinct neighbouring microorganisms but not under standard laboratory conditions. Previously, we provided evidence for such a scenario with the specific activation of the silent ors gene cluster in the filamentous fungus Aspergillus nidulans by the bacterium Streptomyces rapamycinicus. The bacterium triggered the activation of the GcnE histone acetyltransferase that acetylated histone 3 in nucleosomes of the ors gene cluster and the basR transcription factor, and thereby the gene cluster. The inducing compound was shown to be the bacterial arginoketide azalomycin F. Here, by inhibitor studies with the pan-sirtuin inhibitor nicotinamide (NAM) the involvement of a sirtuin HDAC was implied. Accordingly, deletion of all six putative sirtuin-encoding genes (sirA-E and hstA) revealed that only deletion of sirE led to production of orsellinic acid by A. nidulans without the need of the bacterium. Also other effects on growth and colony morphology due to NAM were phenocopied by the sirE deletion mutant. Addition of NAM did not compensate for the loss of the BasR transcription factor required for activation of the ors gene cluster. Collectively, SirE is the negative regulator of the bacteria-induced activation of the ors BGC. In line, addition of NAM to monocultures of Aspergillus mulundensis encoding a sirtuin E with highest similarity to the A. nidulans protein also activated the ors BGC in this fungus.

microbiology↗

bioRxiv2022

Ubiquitous bacterial polyketides induce cross-kingdom microbial interactions

Although the interaction of prokaryotic and eukaryotic microorganisms is critical for the functioning of ecosystems, knowledge of the processes driving microbial interactions within communities is in its infancy. We previously reported that the soil bacterium Streptomyces iranensis specifically triggers the production of natural products in the fungus Aspergillus nidulans. Here, we discovered that arginine-derived polyketides serve as the bacterial signals for this induction. Arginine-derived polyketide-producing bacteria occur world wide. These producer bacteria and the fungi that decode and respond to this signal can be co-isolated from the same soil sample. Arginine-derived polyketides impact surrounding microorganisms both directly as well as indirectly, by inducing the production of natural products in fungi that further influence the composition of microbial consortia. One-Sentence SummaryUbiquitous bacterial polyketides are universal components of the chemical network for microbial communication

microbiology↗

bioRxiv2019

Human neutrophils produce antifungal extracellular vesicles against Aspergillus fumigatus

Polymorphonuclear granulocytes (PMNs) are indispensable for controlling life-threatening fungal infections. In addition to various effector mechanisms, PMNs also produce extracellular vesicles (EVs). Their contribution to antifungal defense has remained unexplored. We reveal that the clinically important human pathogenic fungus Aspergillus fumigatus triggers PMNs to release a distinct set of antifungal EVs (afEVs). Proteome analyses indicated that afEVs are enriched in antimicrobial proteins. The cargo and release kinetics of EVs are modulated by the fungal strain confronted. Tracking of afEVs indicated that they associated with fungal cells and even entered fungal hyphae, resulting in alterations in the morphology of the fungal cell wall and dose-dependent antifungal effects. Two human proteins enriched in afEVs, cathepsin G and azurocidin, were heterologously expressed in fungal hyphae, which led to reduced fungal growth relative to a control retinol binding protein 7 producing strain. In conclusion, the production of afEVs by PMNs offers an intriguing, previously overlooked mechanism of antifungal defense against A. fumigatus. ImportanceInvasive fungal infections caused by the mold Aspergillus fumigatus are a growing concern in the clinic due to the increasing use of immunosuppressive therapies and increasing antifungal drug resistance. These infections result in high mortality as treatment and diagnostic options remain limited. In healthy individuals, neutrophilic granulocytes are critical for elimination of A. fumigatus from the host; however, the exact extracellular mechanism of neutrophil-mediated antifungal activity remains unresolved. Here, we present a mode of antifungal defense employed by human neutrophils against A. fumigatus not previously described. We find that extracellular vesicles produced by neutrophils in response to A. fumigatus infection are able to associate with the fungus, limit growth, and elicit cell damage by delivering antifungal cargo. In the end, antifungal extracellular vesicle biology provides a significant step forward in our understanding of A. fumigatus host pathogenesis and opens up novel diagnostic and therapeutic possibilities.

microbiology↗

bioRxiv2017

Bacterium-triggered remodeling of chromatin identifies BasR, a novel regulator of fungal natural product biosynthesis

The eukaryotic epigenetic machinery is targeted by bacteria to reprogram the response of eukaryotes during their interaction with microorganisms. In line, we discovered that the bacterium Streptomyces rapamycinicus triggered increased chromatin acetylation and thus activation of the silent secondary metabolism ors gene cluster leading to the production of orsellinic acid in the fungus Aspergillus nidulans. Using this model we aim at understanding molecular mechanisms of communication between bacteria and eukaryotic microorganisms based on bacteria-triggered chromatin modification. By genome-wide ChIP-seq analysis of acetylated histone H3 (H3K9ac, H3K14ac) we uncovered the unique chromatin landscape in A. nidulans upon co-cultivation with S. rapamycinicus. Genome-wide acetylation of H3K9 correlated with increased gene expression, whereas H3K14 appears to function in transcriptional initiation by providing a docking side for regulatory proteins. In total, histones belonging to six secondary metabolism gene clusters showed higher acetylation during co-cultivation including the ors, aspercryptin, cichorine, sterigmatocystin, anthrone and 2,4-dihydroxy-3-methyl-6-(2-oxopropyl)benzaldehyde gene cluster with the emericellamide cluster being the only one with reduced acetylation and expression. Differentially acetylated histones were also detected in genes involved in amino acid and nitrogen metabolism, signaling, and genes encoding transcription factors. In conjunction with LC-MS/MS and MALDI-MS imaging, molecular analyses revealed the cross-pathway control and Myb-like transcription factor BasR as regulatory nodes for transduction of the bacterial signal in the fungus. The presence of basR in other fungal species allowed forecasting the inducibility of ors-like gene clusters by S. rapamycinicus in these fungi, and thus their effective interaction with activation of otherwise silent gene clusters.

microbiology↗