Biology subjects

Bulet, P.

Publications and source records attributed to Bulet, P..

4 recordsLinked to original sources

bioRxiv2025

Distinct Bomanins at the Drosophila 55C locus function in resistance and resilience to infections

Host defense against many Gram-positive bacteria and fungal pathogens is mainly provided by the Toll-dependent systemic immune response in Drosophila. While antimicrobial peptides active against these categories of pathogens contribute only modestly to protection, Bomanin peptides are major effectors of the Toll pathway. Remarkably, flies deleted for the 55C locus that contains 10 Bomanin genes are as sensitive as Toll pathway mutant flies to these infections. Yet, the exact functions of single Bomanins in resistance or resilience to infections remain poorly characterized. Here, we have extensively studied the role of these Bomanin genes. BomT1 functions in resistance to Enterococcus faecalis while playing a role in resilience against Metarhizium robertsii infection, like BomS2. BomT1 and BomT2 prevent the dissemination of Candida albicans throughout the host, even though they are not sufficient to confer protection to immunodeficient flies against this pathogen in survival experiments. Furthermore, BomT1 and BomBc1 mutants are sensitive to an Aspergillus fumigatus ribotoxin. We conclude that 55C Bomanins have defined albeit sometimes overlapping roles in the different facets of host defense against infections.

immunology↗

bioRxiv2022

The Toll pathway mediates Drosophila resilience to Aspergillus mycotoxins through specific Bomanins

Host defense against infections encompasses resistance, which targets microorganisms for neutralization or elimination, and resilience/disease tolerance, which allows the host to withstand/tolerate pathogens and repair damages. In Drosophila, the Toll signaling pathway is thought to mediate resistance against fungal infections by regulating the secretion of antimicrobial peptides, potentially including Bomanins. We found that Aspergillus fumigatus kills Drosophila Toll pathway mutants without invasion because its dissemination is blocked by melanization, suggesting a role for Toll in host defense distinct from resistance. We report that mutants affecting the Toll pathway or the 55C Bomanin locus were susceptible to the injection of two Aspergillus mycotoxins, restrictocin or verruculogen. The vulnerability of 55C deletion mutants to these mycotoxins was rescued by the overexpression of Bomanins specific to each challenge. Mechanistically, flies in which BomS6 was expressed in the nervous system exhibited an enhanced recovery from the tremors induced by injected verruculogen and displayed improved survival. Thus, innate immunity also protects the host against the action of microbial toxins through secreted peptides and thereby increase its resilience to infection.

immunology↗

bioRxiv2020

The BaramicinA gene is required at several steps of the host defense against Enterococcus faecalis and Metarhizium robertsii in a septic wound infection model in Drosophila melanogaster

The Drosophila systemic immune response against many Gram-positive bacteria and fungi is mediated by the Toll pathway. How Toll-regulated effectors actually fulfill this role remains poorly understood as the known antimicrobial peptide (AMP) genes it controls are essentially active only against filamentous fungi and not against Gram-positive bacteria or yeasts. BaramicinA gene expression is transcriptionally regulated by the Toll pathway. BaraA encodes a polyprotein precursor that releases processed proteins into the hemolymph upon immune challenge. Here, we demonstrate that BaraA is required specifically in the host defense against Enterococcus faecalis and against the entomopathogenic fungus Metarhizium robertsii. It does so by protecting the fly from the action of distinct toxins secreted by Gram-positive and fungal pathogens but not by directly attacking them. Thus, in complement to the current paradigm, innate immunity can cope with toxins, effectively, through the secretion of peptides that are not AMPs, independently of xenobiotics detoxification pathways.

immunology↗

bioRxiv2019

The antimicrobial peptide Defensin cooperates with Tumour Necrosis Factor to drive tumour cell death in Drosophila

Antimicrobial peptides (AMPs) are small cationic molecules best known as mediators of the innate defence against microbial infection. While in vitro and ex vivo evidence suggest AMPs capacity to kill cancer cells, in vivo demonstration of an anti-tumour role of endogenous AMPs is lacking. Using a Drosophila model of tumourigenesis, we demonstrate a role for the AMP Defensin in the control of tumour progression. Our results reveal that Tumour Necrosis Factor mediates exposure of phosphatidylserine (PS), which makes tumour cells selectively sensitive to the action of Defensin remotely secreted from tracheal and fat tissues. Defensin binds tumour cells in PS-enriched areas, provoking cell death and tumour regression. Altogether, our results provide the first in vivo demonstration for a role of an endogenous AMP as an anti-cancer agent, as well as a mechanism that explains tumour cell sensitivity to the action of AMPs.

cancer biology↗