AN ENTOMOPATHOGENIC BACTERIUM, <i>Xenorhabdus nematophila</i>, SUPPRESSES EXPRESSION OF ANTIMICROBIAL PEPTIDES CONTROLLED BY TOLL AND IMD PATHWAYS BY BLOCKING EICOSANOID BIOSYNTHESIS

Hwang, Jang Yeon; Park, Youngjin; Kim, Yonggyun; Lee, Dae‐Weon

doi:10.1002/arch.21103

Cited by 65 publications

(59 citation statements)

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“…A major component of the insect innate immune response is AMP production by the fat body, a structure similar to the mammalian liver and adipose tissue (44). Studies of a number of insects, including the cecropia moth Hyalophora cecropia, the beet armyworm Spodoptera exigua, and the tobacco hornworm Manduca sexta have shown that EPN infection can induce expression of AMP genes and that both the nematode and the bacteria can suppress AMP activity (45)(46)(47)(48)(49). We previously showed that infection of D. melanogaster larvae with H. bacteriophora symbiont IJs resulted in expression of four AMP genes, attacin, diptericin, drosomycin, and metchnikowin, and that this expression was a specific response to P. luminescens (4).…”

Section: Resultsmentioning

confidence: 99%

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

2015

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Entomopathogenic nematodes (EPNs) in the genera Heterorhabditis and Steinernema are lethal parasites of insects that are of interest as models for understanding parasite-host interactions and as biocontrol agents for insect pests. EPNs harbor a bacterial endosymbiont in their gut that assists in insect killing. EPNs are capable of infecting and killing a wide range of insects, yet how the nematodes and their bacterial endosymbionts interact with the insect immune system is poorly understood. Here, we develop a versatile model system for understanding the insect immune response to parasitic nematode infection that consists of seven species of EPNs as model parasites and five species of Drosophila fruit flies as model hosts. We show that the EPN Steinernema carpocapsae, which is widely used for insect control, is capable of infecting and killing D. melanogaster larvae. S. carpocapsae is associated with the bacterium Xenorhabdus nematophila, and we show that X. nematophila induces expression of a subset of antimicrobial peptide genes and suppresses the melanization response to the nematode. We further show that EPNs vary in their virulence toward D. melanogaster and that Drosophila species vary in their susceptibilities to EPN infection. Differences in virulence among different EPN-host combinations result from differences in both rates of infection and rates of postinfection survival. Our results establish a powerful model system for understanding mechanisms of host-parasite interactions and the insect immune response to parasitic nematode infection. E ntomopathogenic nematodes (EPNs) of the genera Steinernema and Heterorhabditis are insect-parasitic nematodes that are phylogenetically distant but share a similar life cycle as a result of convergent evolution (1). EPNs offer numerous advantages as model parasitic nematodes, including small size, short generation time, and amenability to in vitro culturing (2). EPN infective larvae are associated with bacterial endosymbionts: Steinernema species are associated with bacteria in the genus Xenorhabdus, and Heterorhabditis species are associated with bacteria in the genus Photorhabdus (1). At least some EPNs are capable of infecting the fruit fly Drosophila melanogaster, providing a genetically tractable system for understanding the immune response to parasitic nematodes and their bacterial endosymbionts (3-6). However, the insect immune response to EPN infection is poorly understood.During a particular developmental stage called the infective juvenile (IJ), EPNs infect insects (Fig. 1A). IJs are developmentally arrested, third-stage larvae analogous to the dauer stage of freeliving nematodes (7). IJs actively seek out insect hosts using chemosensory cues (8-10) and infect either by entering through natural body openings or by penetrating the insect cuticle (11). IJs harbor their bacterial endosymbiont in their gut and deposit it into the insect upon infection, where it assists the nematode in killing the insect, digesting insect tissues, and inhibiting the growth of o...

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Section: Resultsmentioning

confidence: 99%

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

2015

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“…For example, early induction of high levels of virulence factors may be recognized by host immune surveillance systems or may cause tissue damage, both of which would trigger an immune response. X. nematophila is adept at escaping host immunity through the production of several immunosuppressive compounds (12,16), in part through the expression of genes controlled by the transcription factor Lrp (4,20). Nonetheless, constitutive overexpression of this transcription factor is detrimental to immune suppression and virulence in M. sexta (23).…”

Section: Discussionmentioning

confidence: 99%

“…The latter finding is based on the facts that heat-killed X. nematophila is recognized by immune surveillance systems and induces AMP expression (4,12,13) and that when wild-type X. nematophila is coinjected with an immunogenic bacterial strain it prevents induction of AMP expression (4). X. nematophila can inhibit phagocytosis and nodulation by secreting phospholipase A 2 (PLA 2 ) inhibitors (5,6,8,9,(14)(15)(16).…”

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confidence: 99%

“…PLA 2 catalyzes the first step in the biosynthesis of eicosanoids (17), which mediate several cellular activities, including immune signaling pathways (18). Coinjection of immunogenic heat-killed X. nematophila and benzylideneacetone (BZA; a PLA 2 inhibitor produced by X. nematophila) suppressed AMP expression in the lepidopteran insect Spodoptera exigua, indicating that eicosanoid pathway inhibition is sufficient to suppress AMP induction in Lepidoptera (12).…”

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confidence: 99%

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The Global Transcription Factor Lrp Is both Essential for and Inhibitory to Xenorhabdus nematophila Insecticidal Activity

Casanova-Torres

Shokal

Morag

et al. 2017

Appl Environ Microbiol

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In the entomopathogenic bacterium Xenorhabdus nematophila, cell-tocell variation in the abundance of the Lrp transcription factor leads to virulence modulation; low Lrp levels are associated with a virulent phenotype and suppression of antimicrobial peptides (AMPs) in Manduca sexta insects, while cells that lack lrp or express high Lrp levels are virulence attenuated and elicit AMP expression. To better understand the basis of these phenotypes, we examined X. nematophila strains expressing fixed Lrp levels. Unlike the lrp-null mutant, the high-lrp strain is fully virulent in Drosophila melanogaster, suggesting that these two strains have distinct underlying causes of virulence attenuation in M. sexta. Indeed, the lrp-null mutant was defective in cytotoxicity against M. sexta hemocytes relative to that in the high-lrp and low-lrp strains. Further, supernatant derived from the lrp-null mutant but not from the high-lrp strain was defective in inhibiting weight gain when fed to 1st instar M. sexta. These data suggest that contributors to the lrp-null mutant virulence attenuation phenotype are the lack of Lrp-dependent cytotoxic and extracellular oral growth inhibitory activities, which may be particularly important for virulence in D. melanogaster. In contrast, the high-Lrp strain was sensitive to the antimicrobial peptide cecropin, had a transient survival defect in M. sexta, and had reduced extracellular levels of insecticidal activity, measured by injection of supernatant into 4th instar M. sexta. Thus, high-lrp strain virulence attenuation may be explained by its hypersensitivity to M. sexta host immunity and its inability to secrete one or more insecticidal factors.IMPORTANCE Adaptation of a bacterial pathogen to host environments can be achieved through the coordinated regulation of virulence factors that can optimize success under prevailing conditions. In the insect pathogen Xenorhabdus nematophila, the global transcription factor Lrp is necessary for virulence when injected into Manduca sexta or Drosophila melanogaster insect hosts. However, high levels of Lrp, either naturally occurring or artificially induced, cause attenuation of X. nematophila virulence in M. sexta but not D. melanogaster. Here, we present evidence suggesting that the underlying cause of high-Lrp-dependent virulence attenuation in M. sexta is hypersensitivity to host immune responses and decreased insecticidal activity and that high-Lrp virulence phenotypes are insect host specific. This knowledge suggests that X. nematophila faces varied challenges depending on the type of insect host it infects and that its success in these environments depends on Lrp-dependent control of a multifactorial virulence repertoire.

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“…Hemocyte and gut transcriptomes were generated by 454 pyrosequencing (Hwang et al, 2013). A mixed transcriptome of S. exigua was generated using different tissues under different stress conditions (Pascual et al, 2012).…”

Section: Polyol Analysis Using Hplcmentioning

confidence: 99%

RNA interference of glycerol biosynthesis suppresses rapid cold hardening of the beet armyworm,Spodoptera exigua

Park

Kim

2013

Journal of Experimental Biology

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SUMMARYThe beet armyworm, Spodoptera exigua, is a freeze-susceptible species that overwinters in temperate zones without diapause. A rapid cold hardening (RCH) and supercooling capacity usually play crucial roles in survival during the overwintering period. This study identified a cryoprotectant as a RCH factor of S. exigua. Pre-exposure of S. exigua larvae to 4°C significantly increased survival at −10°C in all developmental stages from egg to adult. RCH was dependent on the duration of the pre-exposure period. RCH also significantly enhanced the supercooling capacity. Cryoprotectant analysis using HPLC showed that the pre-exposure treatment allowed the larvae to accumulate glycerol in the hemolymph. Two genes, glycerol-3-phosphate dehydrogenase (GPDH) and glycerol kinase (GK), were identified as being associated with glycerol biosynthesis, and were cloned from S. exigua larvae. Both GPDH and GK were expressed in all developmental stages of S. exigua. RNA interference (RNAi) of either GPDH or GK significantly inhibited glycerol accumulation in the hemolymph of S. exigua. Larvae treated with RNAi for GPDH or GK exhibited a significant decrease in RCH capacity. The glycerol accumulation in response to 4°C appeared to be under the control of a humoral signal, because a ligation experiment prevented glycerol accumulation in the other half of the body. This study indicates that glycerol is a RCH factor of S. exigua and its synthesis is in response to low temperature via humoral mediation. Supplementary material available online at

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AN ENTOMOPATHOGENIC BACTERIUM, Xenorhabdus nematophila, SUPPRESSES EXPRESSION OF ANTIMICROBIAL PEPTIDES CONTROLLED BY TOLL AND IMD PATHWAYS BY BLOCKING EICOSANOID BIOSYNTHESIS

Cited by 65 publications

References 52 publications

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

The Global Transcription Factor Lrp Is both Essential for and Inhibitory to Xenorhabdus nematophila Insecticidal Activity

RNA interference of glycerol biosynthesis suppresses rapid cold hardening of the beet armyworm,Spodoptera exigua

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