Candida albicans Induces Cross-Kingdom miRNA Trafficking in Human Monocytes To Promote Fungal Growth

Halder, Luke D.; Babych, Svitlana; Palme, Diana I; Mansouri-Ghahnavieh, Elham; Ivanov, Lia; Ashonibare, Victory; Langenhorst, Daniela; Prusty, Bhupesh K.; Rambach, Günter; Wich, Melissa; Trinks, Nora; Blango, Matthew G.; Kornitzer, Daniel; Terpitz, Ulrich; Speth, Cornelia; Jungnickel, Berit; Beyersdorf, Niklas; Zipfel, Peter F.; Brakhage, Axel A.; Skerka, Christine

doi:10.1128/mbio.03563-21

Cited by 24 publications

(18 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a branch of this pathway, STE7 inhibited the CKI protein MpCKI by phosphorylation through the Fus3 MAPK pathway (Bhattacharyya et al 2006 ). These results further highlighted these cell-cycle elements for signaling networks involved in fungal morphogenesis (Halder et al 2021 ).…”

Section: Discussionsupporting

confidence: 60%

The serine/threonine protein kinase MpSTE1 directly governs hyphal branching in Monascus spp.

Duan,

Chen,

Wang

et al. 2024

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

Monascus spp. are commercially important fungi due to their ability to produce beneficial secondary metabolites such as the cholesterol-lowering agent lovastatin and natural food colorants azaphilone pigments. Although hyphal branching intensively influenced the production of these secondary metabolites, the pivotal regulators of hyphal development in Monascus spp. remain unclear. To identify these important regulators, we developed an artificial intelligence (AI)–assisted image analysis tool for quantification of hyphae-branching and constructed a random T-DNA insertion library. High-throughput screening revealed that a STE kinase, MpSTE1, was considered as a key regulator of hyphal branching based on the hyphal phenotype. To further validate the role of MpSTE1, we generated an mpSTE1 gene knockout mutant, a complemented mutant, and an overexpression mutant (OE::mpSTE1). Microscopic observations revealed that overexpression of mpSTE1 led to a 63% increase in branch number while deletion of mpSTE1 reduced the hyphal branching by 68% compared to the wild-type strain. In flask cultures, the strain OE::mpSTE1 showed accelerated growth and glucose consumption. More importantly, the strain OE::mpSTE1 produced 9.2 mg/L lovastatin and 17.0 mg/L azaphilone pigments, respectively, 47.0% and 30.1% higher than those of the wild-type strain. Phosphoproteomic analysis revealed that MpSTE1 directly phosphorylated 7 downstream signal proteins involved in cell division, cytoskeletal organization, and signal transduction. To our best knowledge, MpSTE1 is reported as the first characterized regulator for tightly regulating the hyphal branching in Monascus spp. These findings significantly expanded current understanding of the signaling pathway governing the hyphal branching and development in Monascus spp. Furthermore, MpSTE1 and its analogs were demonstrated as promising targets for improving production of valuable secondary metabolites. Key points • MpSTE1 is the first characterized regulator for tightly regulating hyphal branching • Overexpression of mpSTE1 significantly improves secondary metabolite production • A high-throughput image analysis tool was developed for counting hyphal branching

show abstract

Section: Discussionsupporting

confidence: 60%

The serine/threonine protein kinase MpSTE1 directly governs hyphal branching in Monascus spp.

Duan,

Chen,

Wang

et al. 2024

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…Small RNA-mediated RNA interference (RNAi) is a conserved eukaryotic gene-silencing mechanism. Accumulating evidence has shown that sRNAs can not only regulate gene expression in the same cells, but they can also travel between interacting organisms to induce gene silencing in trans, which is called cross-kingdom or cross-species RNAi (Halder et al ., 2022, Wong-Bajracharya et al, 2022, Cui et al, 2019, Ren et al, 2019, Dunker et al, 2020, Shahid et al, 2018, Ji et al, 2021, Zhang et al, 2022, Buck et al, 2014, Chow et al, 2019, Sahr et al, 2022). Recently, Qin et al .…”

Section: Discussionmentioning

confidence: 99%

Botrytis cinereasmall RNAs are associated with tomato AGO1 and silence tomato defense-related target genes supporting cross-kingdom RNAi

Cai

Weiberg

et al. 2023

Preprint

View full text Add to dashboard Cite

Cross-kingdom or cross-species RNA interference (RNAi) is broadly present in many interacting systems between microbes/parasites and their plant and animal hosts. Recent study by Qin et al. (2022) performed correlation analysis using global sRNA- and mRNA-deep sequencing data of cultured B. cinerea and B. cinerea-infected tomato leaves and claimed that cross kingdom RNAi may not occur in B. cinerea tomato interaction (Qin et al., 2022). In this response letter, we use experimental evidence and additional bioinformatics analysis of the datasets produced by Qin et al. (2022) to identify the key reasons why a discrepancy with previously published findings occurred. Here, we also provided additional experimental evidence to support the presence of cross-kingdom RNAi between tomato and B. cinerea. We believe it is important to clarify the basic concept and mechanism of cross-kingdom/cross-species sRNA trafficking and illustrate proper bioinformatics analyses in this regard for all the scientists and researchers in this field.

show abstract

“…Currently, cross-kingdom regulation between insects and fungal pathogens is poorly understood. As key regulators in regulating gene expression and biological processes, miRNAs have been verified to mediate cross-kingdom regulation among animals, plants, and microorganisms ( Halder et al, 2022 ; Rabuma et al, 2022 ). During the infection of Solanum lycopersicum and Aedes albopictus , Botrytis cinerea and Beauveria bassiana can synthesize and secrete sRNAs into the host cell via vesicles and hijack the RNA interference mechanism by binding to the Argonaute 1 protein, which further silenced the expression of host immune genes ( Weiberg et al, 2013 ; Cui et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

In-depth investigation of microRNA-mediated cross-kingdom regulation between Asian honey bee and microsporidian

Fan

Zhang

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

Asian honey bee Apis cerana is the original host for Nosema ceranae, a unicellular fungal parasite that causes bee nosemosis throughout the world. Currently, interaction between A. cerana and N. ceranae is largely unknown. Our group previously prepared A. c. cerana workers’ midguts at 7 days post inoculation (dpi) and 10 dpi with N. ceranae spores as well as corresponding un-inoculated workers’ midguts, followed by cDNA library construction and a combination of RNAs-seq and small RNA-seq. Meanwhile, we previously prepared clean spores of N. ceranae, which were then subjected to cDNA library construction and deep sequencing. Here, based on the gained high-quality transcriptome datasets, N. ceranae differentially expressed mRNAs (DEmiRNAs) targeted by host DEmiRNAs, and A. c. cerana DEmRNAs targeted by microsporidian DEmiRNAs were deeply investigated, with a focus on targets involved in N. ceranae glycolysis/glyconeogenesis as well as virulence factors, and A. c. cerana energy metabolism and immune response. In A. c. cerana worker’s midguts at 7 (10) dpi (days post inoculation), eight (seven) up-regulated and six (two) down-regulated miRNAs were observed to target 97 (44) down-regulated and 60 (15) up-regulated N. ceranae mRNAs, respectively. Additionally, two up-regulated miRNAs (miR-60-y and miR-676-y) in host midgut at 7 dpi could target genes engaged in N. ceranae spore wall protein and glycolysis/gluconeogenesis, indicating potential host miRNA-mediated regulation of microsporidian virulence factor and energy metabolism. Meanwhile, in N. ceranae at 7 (10) dpi, 121 (110) up-regulated and 112 (104) down-regulated miRNAs were found to, respectively, target 343 (247) down-regulated and 138 (110) down-regulated mRNAs in A. c. cerana workers’ midguts. These targets in host were relevant to several crucial cellular and humoral immune pathways, such as phagasome, endocytosis, lysosomes, regulation of autophagy, and Jak–STAT signaling pathway, indicative of the involvement of N. ceranae DEmiRNAs in regulating these cellular and humoral immune pathways. In addition, N. ceranae miR-21-x was up-regulated at 7 dpi and had a target relative to oxidative phosphorylation, suggesting that miR-21-x may be used as a weapon to modulate this pivotal energy metabolism pathway. Furthermore, potential targeting relationships between two pairs of host DEmiRNAs-microsporidian DEmRNAs and two pairs of microsporidian DEmiRNAs-host DEmRNAs were validated using RT-qPCR. Our findings not only lay a foundation for exploring the molecular mechanism underlying cross-kingdom regulation between A. c. cerana workers and N. ceranae, but also offer valuable insights into Asian honey bee-microsporidian interaction.

show abstract

Candida albicans Induces Cross-Kingdom miRNA Trafficking in Human Monocytes To Promote Fungal Growth

Cited by 24 publications

References 66 publications

The serine/threonine protein kinase MpSTE1 directly governs hyphal branching in Monascus spp.

The serine/threonine protein kinase MpSTE1 directly governs hyphal branching in Monascus spp.

Botrytis cinereasmall RNAs are associated with tomato AGO1 and silence tomato defense-related target genes supporting cross-kingdom RNAi

In-depth investigation of microRNA-mediated cross-kingdom regulation between Asian honey bee and microsporidian

Contact Info

Product

Resources

About