The Daisho Peptides Mediate Drosophila Defense Against a Subset of Filamentous Fungi

Cohen, Lianne B.; Lindsay, Scott A.; Xu, Yangyang; Lin, Samuel; Wasserman, Steven A.

doi:10.3389/fimmu.2020.00009

Cited by 52 publications

(78 citation statements)

References 37 publications

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“…encode Daisho peptides, which were reported to aid defense against specific filamentous fungi (51). CG33470 is an uncharacterized transcript located 3.3 kb downstream of IMPPP and might belong to the same open reading frame, as both are sometimes referred to as IM10 (52), and show nearly identical gene counts in our dataset.…”

Section: Gene Ontology and Gene Set Analysis Demonstrate A Divergencementioning

confidence: 88%

Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response

Schlamp

Delbare

Early

et al. 2020

Preprint

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BackgroundImmune responses need to be initiated rapidly, and maintained as needed, to prevent establishment and growth of infections. At the same time, resources need to be balanced with other physiological processes. On the level of transcription, studies have shown that this balancing act is reflected in tight control of the initiation kinetics and shutdown dynamics of specific immune genes. ResultsTo investigate expression dynamics and trade-offs after infection genome-wide and with high temporal resolution, we performed an RNA-seq time course on D. melanogaster with 20 time points post-LPS injection. A combination of methods, including spline fitting, cluster analysis, and Granger Causality inference, allowed detailed dissection of expression profiles, lead-lag interactions, and functional annotation of genes through guilt-by-association. We identified genes encoding antimicrobial peptides and co-expressed, less well characterized genes, as immediate-early response genes with a sustained up-regulation up to five days after stimulation. In contrast, stress response genes and additional immune genes, among which were Bomanins, demonstrated early and transient responses. We further observed a strong trade-off with metabolic genes, which strikingly recovered to pre-infection levels before the immune response was fully resolved. ConclusionsThis high-dimensional dataset enabled the comprehensive study of immune response dynamics through the parallel application of multiple temporal data analysis methods. Multivariate Granger causality analysis proved to be a valuable addition to classical time course analysis methods such as clustering, due to its ability to define directed networks of lead-lag patterns.

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Section: Gene Ontology and Gene Set Analysis Demonstrate A Divergencementioning

confidence: 88%

Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response

Schlamp

Delbare

Early

et al. 2020

Preprint

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“…In addition, some non-classical AMPs such as Bomanins ( 72 ), Daishos ( 73 ) and Listericin ( 74 ) in Drosophila have also attracted our attention. An effector peptide family encoded by twelve Bomanin ( Bom ) genes has been found to be essential for effective Drosophila Toll-mediated immune responses ( 72 ).…”

Section: Potential Avps In Fruit Fly Honeybee and Silkwormmentioning

confidence: 99%

“…An effector peptide family encoded by twelve Bomanin ( Bom ) genes has been found to be essential for effective Drosophila Toll-mediated immune responses ( 72 ). Daisho peptides, a new class of innate immune effectors in Drosophila , were recently found to have humoral activity against a set of filamentous fungi ( 73 ). Currently, these Drosophila peptides have not been confirmed to have antiviral activity.…”

Section: Potential Avps In Fruit Fly Honeybee and Silkwormmentioning

confidence: 99%

Antimicrobial Peptides as Potential Antiviral Factors in Insect Antiviral Immune Response

et al. 2020

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Antimicrobial peptides (AMPs) with antiviral activity (antiviral peptides: AVPs) have become a research hotspot and already show immense potential to become pharmaceutically available antiviral drugs. AVPs have exhibited huge potential in inhibiting viruses by targeting various stages of their life cycle. Insects are the most speciose group of animals that inhabit almost all ecosystems and habitats on the land and are a rich source of natural AMPs. However, insect AVP mining, functional research, and drug development are still in their infancy. This review aims to summarize the currently validated insect AVPs, explore potential new insect AVPs and to discuss their possible mechanism of synthesis and action, with a view to providing clues to unravel the mechanisms of insect antiviral immunity and to develop insect AVP-derived antiviral drugs.

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“…It is made The copyright holder for this preprint this version posted November 23, 2020. ; https://doi.org/10.1101/2020.11.23.394148 doi: bioRxiv preprint by crossing through the insect cuticle. The Toll pathway is critical to survive fungal pathogens as it is directly responsible for the expression of Bomanins, Daishos, Drosomycin and Metchnikowin antifungal effectors [12,14,15,29,30]. The fact that i)…”

Section: Baraa Mutant Flies Are Highly Susceptible To Fungal Infectionmentioning

confidence: 99%

“…Two other IMs encoding IM4 and IM14 (renamed Daisho1 and Daisho2, respectively) were shown to contribute downstream of Toll to resistance against specific fungi. Interestingly, Daisho peptides bind to fungal hyphae, suggesting direct antifungal activity [14].…”

Section: Introduction (806 Words)mentioning

confidence: 99%

The Drosophila Baramicin polypeptide gene protects against fungal infection

Hanson

Cohen

Marra

et al. 2020

Preprint

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The fruit fly Drososphila melanogaster combats microbial infection by producing a battery of effector peptides that are secreted into the haemolymph. The existence of many effectors that redundantly contribute to host defense has hampered their functional characterization. As a consequence, the logic underlying the role of immune effectors is only poorly defined, and exactly how each gene contributes to survival is not well characterized. Here we describe a novel Drosophila antifungal peptide gene that we name Baramicin A. We show that BaraA encodes a precursor protein cleaved into multiple peptides via furin cleavage sites. BaraA is strongly immune-induced in the fat body downstream of the Toll pathway, but also exhibits expression in the nervous system. Importantly, we show that flies lacking BaraA are viable but susceptible to a subset of filamentous fungi. Consistent with BaraA being directly antimicrobial, overexpression of BaraA promotes resistance to fungi and the IM10-like peptides produced by BaraA synergistically inhibit growth of fungi in vitro when combined with a membrane-disrupting antifungal. Surprisingly, BaraA males but not females display an erect wing phenotype upon infection, pointing to a protective role of BaraA on the wing muscle or the nervous system. Collectively, we identify a new antifungal immune effector downstream of Toll signalling, improving our knowledge of the Drosophila antimicrobial response.

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The Daisho Peptides Mediate Drosophila Defense Against a Subset of Filamentous Fungi

Cited by 52 publications

References 37 publications

Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response

Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response

Antimicrobial Peptides as Potential Antiviral Factors in Insect Antiviral Immune Response

The Drosophila Baramicin polypeptide gene protects against fungal infection

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