Sequential immunosuppressive activities of bacterial secondary metabolites from the entomopahogenic bacterium Xenorhabdus nematophila

Abstract

The entomopathogenic bacterium Xenorhabdus nematophila secretes at least eight bacterial metabolites that play crucial roles suppressing target insect immune responses by inhibiting eicosanoid biosynthesis. We analyzed sequential changes in bacterial metabolite production during bacterial growth and analyzed their individual immunosuppressive activities against the insect host, Spodoptera exigua. X. nematophila exhibited a typical bacterial growth pattern in both insect host and culture medium, and eight metabolites were secreted at different time points. At the early growth phase (6-12 h), Ac-FGV and PHPP were detected in significant amounts in the culture broth. At this early phase, both Ac-FGV (18 μg/ml) and oxindole (110 μg/ml) levels significantly inhibited phenoloxidase and phospholipase A(2) activities in S. exigua hemolymph. At the late growth phase (12-36 h), all eight metabolites were detected at significant levels (10-140 μg/ml) in the culture broth and were sufficient to induce hemocyte toxicity. These results suggest that X. nematophila sequentially produces immunosuppressive metabolites that might sequentially and cooperatively inhibit different steps of insect immune responses.

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

“…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).…”

“…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). PLA 2 catalyzes the first step in the biosynthesis of eicosanoids (17), which mediate several cellular activities, including immune signaling pathways (18).…”

Microbiology of sugar‐rich environments: diversity, ecology and system constraints

“…Insect haemolymph ∼0.99 aw; pH 5.9-8.5; sugar composition is dominated by trehalose and glucose (Buck, 1953;Xylander, 2009;Mayack and Naug, 2010) Volatile components of insect pheromones, as well as secondary metabolites of microbes, can be present (Teal et al, 1999;Subchev and Jurenka, 2001;Reddy and Guerrero, 2004;Eom et al, 2014). A considerable number of bacterial and fungal pathogens, mutualists and symbionts can inhabit the haemolymph of diverse insect species (Charnley, 1990;Vega and Dowd, 2005;Pontes and Dale, 2006;Douglas, 2009).…”

A Technique to Enhance Insecticidal Efficacy Using Bt Cry Toxin Mixture and Eicosanoid Biosynthesis Inhibitor

“…따라서 이 대 상 곤충의 면역작용 억제는 비티의 살충력을 증가시킬 수 있는 연구전략으로 이용되었다 (Rahman et al, 2004;Kwon and Kim, 2007;Broderick et al, 2010). (Eom et al, 2014). 본 연구는 이 두 한계를 극복하기 위해 Cry 독소 단백질의 혼합과 벡큘로바이러스 또는 면역억제물질과 혼용 의 서로 다른 전략들을 세웠다.…”