The Effects of Destruxin A on Relish and Rel Gene Regulation to the Suspected Immune-Related Genes of Silkworm

Hu, Weina; He, Guangwei; Wang, Jingjing; Hu, Qiongbo

doi:10.3390/molecules22010041

Cited by 11 publications

(11 citation statements)

References 19 publications

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“…bassiana as well as B . brongniartii are known to produce several of these compounds [ 52 ]. Whether any of these bioactive compounds are directly affecting these immune signaling pathways in the mosquito remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Entomopathogenic fungal infection leads to temporospatial modulation of the mosquito immune system

et al. 2018

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Alternative methods of mosquito control are needed to tackle the rising burden of mosquito-borne diseases while minimizing the use of synthetic insecticides, which are threatened by the rapid increase in insecticide resistance in mosquito populations. Fungal biopesticides show great promise as potential alternatives because of their ecofriendly nature and ability to infect mosquitoes on contact. Here we describe the temporospatial interactions between the mosquito Aedes aegypti and several entomopathogenic fungi. Fungal infection assays followed by the molecular assessment of infection-responsive genes revealed an intricate interaction between the mosquito immune system and entomopathogenic fungi. We observed contrasting tissue and time-specific differences in the activation of immune signaling pathways and antimicrobial peptide expression. In addition, these antifungal responses appear to vary according to the fungal entomopathogen used in the infection. Enzyme activity-based assays coupled with gene expression analysis of prophenoloxidase genes revealed a reduction in phenoloxidase (PO) activity in mosquitoes infected with the most virulent fungal strains at 3 and 6d post-fungal infection. Moreover, fungal infection led to an increase in midgut microbiota that appear to be attributed in part to reduced midgut reactive oxygen species (ROS) activity. This indicates that the fungal infection has far reaching effects on other microbes naturally associated with mosquitoes. This study also revealed that despite fungal recognition and immune elicitation by the mosquito, it is unable to successfully eliminate the entomopathogenic fungal infection. Our study provides new insights into this intricate multipartite interaction and contributes to a better understanding of mosquito antifungal immunity.

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Section: Discussionmentioning

confidence: 99%

Entomopathogenic fungal infection leads to temporospatial modulation of the mosquito immune system

et al. 2018

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“…For this, it is necessary to elucidate the targets of DA acting on insects. In the past decade, several studies indicated that DA changes the morphology of hemocytes and brings on equilibrium chaos of intra-and extra-cellular hydrogen and calcium ion in Bombyx mori [4,5], and regulates immune related gene expression [6,7]. Recently, a few DA binding-proteins in silkworm were found [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Interactions of Destruxin A with Silkworms’ Arginine tRNA Synthetase and Lamin-C Proteins

Wang¹,

Weng²,

Yin³

et al. 2020

Toxins

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Destruxin A (DA), a cyclodepsipeptidic mycotoxin produced by entomopathogenic fungus Metarhizium anisopliae, has good insecticidal activity and potential to be a new pesticide. However, the mechanism of action is still obscure. Our previous experiments showed that DA was involved in regulation of transcription and protein synthesis and suggested that silkworms’ arginine tRNA synthetase (BmArgRS), Lamin-C Proteins (BmLamin-C) and ATP-dependent RNA helicase PRP1 (BmPRP1) were candidates of DA-binding proteins. In this study, we employed bio-layer interferometry (BLI), circular dichroism (CD), cellular thermal shift assay (CETSA), and other technologies to verify the interaction of DA with above three proteins in vitro and in vivo. The results of BLI indicated that BmArgRS and BmLamin-C were binding-protein of DA with KD value 5.53 × 10−5 and 8.64 × 10−5 M, but not BmPRP1. These interactions were also verified by CD and CETSA tests. In addition, docking model and mutants assay in vitro showed that BmArgRS interacts with DA at the pocket including Lys228, His231, Asp434 and Gln437 in its enzyme active catalysis region, while BmLamin-C binds to DA at His524 and Lys528 in the tail domain. This study might provide new insight and evidence in illustrating molecular mechanism of DA in breaking insect.

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“…This complex has been shown to have a role in pre-messenger RNA splicing from yeast to humans. Previously, we found that DA influences the splicing of pre-mRNA of silkworm’s immune-related gene, BmRelish, and results in expression of BmRelish1 which is higher than that of BmRelish2 [11]. Therefore, we hypothesized that DA might interfere with the interaction of BmPPI with Bmo.3174 and lead to irregularity splicing of the downstream immune-related gene in the immune-related pathway.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, DA has attracted attention for its immunosuppressant activity. It has been reported that DA impacts antimicrobial peptides in Drosophila melanogaster [10], regulates the gene expression of BmRelish and BmRel of the Imd pathway in Bombyx mori [11], and influences the expression of immunity-related genes in insects [12,13,14]. However, there has been no significant progress on clarifying the molecular toxicology of DA.…”

Section: Introductionmentioning

confidence: 99%

Effects of Destruxin A on Silkworm’s Immunophilins

Wang

Weng

2019

Toxins

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Destruxin A (DA), a major secondary metabolite of Metarhizium anisopliae, has anti-immunity to insects. However, the detailed mechanism and its interactions with target proteins are elusive. Previously, three immunophilins, peptidyl–prolyl cis–trans isomerase (BmPPI), FK506 binding-protein 45 (BmFKBP45) and BmFKBP59 homologue, were isolated from the silkworm, Bombyx mori Bm12 cell line following treatment with DA, which suggested that these proteins were possible DA-binding proteins. To validate the interaction between DA and the three immunophilins, we performed bio-layer interferometry (BLI) assay, and the results showed that DA has interaction with BmPPI, whose affinity constant value is 1.98 × 10−3 M and which has no affinity with FKBP45 and FKBP59 homologue in vitro. Furthermore, we investigated the affinity between DA and human PPI protein (HsPPIA) and the affinity constant (KD) value is 2.22 × 10−3 M. Additionally, we compared the effects of silkworm and human PPI proteins produced by DA and immunosuppressants, cyclosporine A (CsA), and tacrolimus (FK506), by employing I2H (insect two-hybrid) in the SF-9 cell line. The results indicated that in silkworm, the effects created by DA and CsA were stronger than FK506. Furthermore, the effects created by DA in silkworm were stronger than those in humans. This study will offer new thinking to elucidate the molecular mechanism of DA in the immunity system of insects.

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The Effects of Destruxin A on Relish and Rel Gene Regulation to the Suspected Immune-Related Genes of Silkworm

Cited by 11 publications

References 19 publications

Entomopathogenic fungal infection leads to temporospatial modulation of the mosquito immune system

Entomopathogenic fungal infection leads to temporospatial modulation of the mosquito immune system

Interactions of Destruxin A with Silkworms’ Arginine tRNA Synthetase and Lamin-C Proteins

Effects of Destruxin A on Silkworm’s Immunophilins

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