The Genetic Basis of Natural Variation in Drosophila melanogaster Immune Defense against Enterococcus faecalis

Chapman, J. R.; Dowell, Maureen A.; Chan, Rosanna; Unckless, Robert L.

doi:10.3390/genes11020234

Cited by 19 publications

(31 citation statements)

References 73 publications

(99 reference statements)

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“…Indeed, several genes have been identified by genome-wide association studies on E. faecalis and entomopathogenic fungi (Chapman et al, 2020;Wang et al, 2017).In addition, we did not observe any protection conferred by the transgenic overexpression of BaraA, in wild-type or MyD88 background. It is thus likely that BaraA acts in conjunction with other Toll pathwayinduced genes.…”

Section: Is Baraa Acting Alone In Host Defense?contrasting

confidence: 61%

“…Interestingly, this protein appears to be involved both in resistance, through the stabilization of BomS peptides in the hemolymph and in resilience, because of a detrimental effect of BomS peptides in its absence. Finally, flies for which the expression of BomBc1 is attenuated by RNAi have been reported to be sensitive to E. faecalis infection (Chapman et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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A Toll pathway effector protectsDrosophilaspecifically from distinct toxins secreted by a fungus or a bacterium

Hunag

Lou

Liu

et al. 2020

Preprint

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The host defense against several Gram-positive bacterial and fungal infections is mostly mediated by the Toll pathway in Drosophila, which regulates the expression of multiple genes including effectors of the innate immune response. One such potential effector is IMPPP/BaraA, a precursor protein that is processed at furin cleavage sites into an armamentarium of small DIM peptides that display a high degree of sequence similarity. We report here the generation of multiple mutants affecting this gene. Our phenotypic analysis revealed a specific sensitivity to pathogens belonging to distinct kingdoms, the Gram-positive bacterium Enterococcus faecalis and the entomopathogenic fungus Metarhizium anisopliae, only in septic injury models of infection. Unexpectedly, we failed to reveal a consistently increased microbial burden in the mutant flies infected with either of these microorganisms, opening the possibility for a role of BaraA in resilience rather than in resistance, which we were however unable to confirm. We also found that some BaraA-derived DIM peptides display an antimicrobial activity at millimolar concentrations in vitro. BaraA is additionally required for an efficient cleavage of pro-phenol oxidase into an active enzyme. BaraA is also involved in the cellular host defense, but through distinct mechanisms: it needs to be expressed in hemocytes for an efficient response solely to E. faecalis infection whereas it is required for the uptake by plasmatocytes of M. robertsii conidia. We propose a model whereby BaraA secreted by hemocytes may act at a very short range and protect host tissues or organs targeted specifically by E. faecalis. This study thus reveals an unexpected functional complexity of a potential effector of the Toll pathway in the host defense against specific infections.

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Section: Is Baraa Acting Alone In Host Defense?contrasting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

A Toll pathway effector protectsDrosophilaspecifically from distinct toxins secreted by a fungus or a bacterium

Hunag

Lou

Liu

et al. 2020

Preprint

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“…While C. burnetii is not a natural D. melanogaster pathogen, there is evidence that it is an endosymbiont of tick arthropods and may have co-evolved in these animals ( Duron et al 2015 ). Previous studies show that few genome-wide significant variants are identified when using a non-natural versus natural D. melanogaster pathogen ( Magwire et al 2012 ), or when the pathogen has low prevalence in D. melanogaster ( Chapman et al 2020 ). Similarly, our GWA analyses did not identify any variants that met the expected Bonferonni-corrected P -value significance level.…”

Section: Discussionmentioning

confidence: 99%

Natural genetic variation inDrosophila melanogasterreveals genes associated withCoxiella burnetiiinfection

et al. 2021

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The gram-negative bacterium Coxiella burnetii is the causative agent of Query (Q) fever in humans and coxiellosis in livestock. Host genetics are associated with Coxiella burnetii pathogenesis both in humans and animals; however, it remains unknown if specific genes are associated with severity of infection. We employed the Drosophila Genetics Reference Panel to perform a genome-wide association study to identify host genetic variants that affect host survival to Coxiella burnetii infection. The genome-wide association study identified 64 unique variants (P < 10−5) associated with 25 candidate genes. We examined the role each candidate gene contributes to host survival during Coxiella burnetii infection using flies carrying a null mutation or RNAi knockdown of each candidate. We validated 15 of the 25 candidate genes using at least one method. This is the first report establishing involvement of many of these genes or their homologs with Coxiella burnetii susceptibility in any system. Among the validated genes, FER and tara play roles in the JAK/STAT, JNK, and decapentaplegic/TGF-β signaling pathways which are components of known innate immune responses to Coxiella burnetii infection. CG42673 and DIP-ε play roles in bacterial infection and synaptic signaling but have no previous association with Coxiella burnetii pathogenesis. Furthermore, since the mammalian ortholog of CG13404 (PLGRKT) is an important regulator of macrophage function, CG13404 could play a role in host susceptibility to Coxiella burnetii through hemocyte regulation. These insights provide a foundation for further investigation regarding the genetics of Coxiella burnetii susceptibility across a wide variety of hosts.

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“…These bacteria are reported to be extracted from Drosophila melanogaster and are considered as a natural pathogen for the fruit flies [ 29 , 30 ]. A day before infections, primary culture was set up by inoculating a small amount of bacterial inoculum from a cryovial into 10 mL of LB medium.…”

Section: Methodsmentioning

confidence: 99%

“…Larvae from both the regimes were grown at high and low larval densities, and we subsequently measured their survivorship post infection in adult stage with either a gram-negative bacterium Pseudomonas entomophila or a gram-positive bacterium Enterococcus faecalis . Along with causing severe damage to the gut, both the bacteria are known to cause systemic pathogenic infection [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Evolution of pathogen-specific improved survivorship post-infection in populations of Drosophila melanogaster adapted to larval crowding

et al. 2021

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The environment experienced by individuals during their juvenile stages has an impact on their adult stages. In holometabolous insects like Drosophila melanogaster, most of the resource acquisition for adult stages happens during the larval stages. Larval-crowding is a stressful environment, which exposes the larvae to scarcity of food and accumulation of toxic waste. Since adult traits are contingent upon larval stages, in larval-crowding like conditions, adult traits are prone to get affected. While the effect of resource limited, poor-developmental environment on adult immune response has been widely studied, the effect of adaptation to resource-limited developmental environment has not been studied, therefore in this study we assayed the evolution of ability to survive infection in adult stages as a correlated response to adaptation to larval crowding environments. Using four populations of Drosophila melanogaster adapted to larval crowding for 240 generations and their respective control populations, we show that populations adapted to larval crowding show an improved and evolved post-infection survivorship against a gram-negative bacteria Pseudomonas entomophila. Whereas, against a gram-positive bacteria Enterococcus faecalis, no difference in post-infection survivorship was observed across control and selected populations. In this study, we report the co-related evolution of pathogen-specific increased survivorship post-infection in populations of Drosophila melanogaster as a result of adaptation to larval crowding environment.

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The Genetic Basis of Natural Variation in Drosophila melanogaster Immune Defense against Enterococcus faecalis

Cited by 19 publications

References 73 publications

A Toll pathway effector protectsDrosophilaspecifically from distinct toxins secreted by a fungus or a bacterium

A Toll pathway effector protectsDrosophilaspecifically from distinct toxins secreted by a fungus or a bacterium

Natural genetic variation inDrosophila melanogasterreveals genes associated withCoxiella burnetiiinfection

Evolution of pathogen-specific improved survivorship post-infection in populations of Drosophila melanogaster adapted to larval crowding

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