An entomopathogenic bacterium, Xenorhabdus nematophila, inhibits hemocytic phospholipase A2 (PLA2) in tobacco hornworms Manduca sexta

Abstract

The entomopathogenic bacterium, Xenorhabdus nematophila, induces immunodepression in target insects and finally leads to lethal septicemia of the infected hosts. A hypothesis has been raised that the bacteria inhibit eicosanoid-biosynthesis pathway to interrupt immune signaling of the infected hosts. Here, we show direct evidence that X. nematophila inhibits the activity of phospholipase A2 (PLA2), the initial step in the eicosanoid-biosynthesis pathway. Inhibition of PLA2 was dependent on both incubation time with X. nematophila and the bacterial concentration in in vitro PLA2 preparations of Manduca sexta hemocytes. While living bacteria inhibited PLA2 activity, heat-killed X. nematophila rather increased PLA2 activity. X. nematophila secreted PLA2 inhibitor(s), which were detected in the organic, but not aqueous, extract of the bacterial culture medium. The PLA2 inhibitory activity of the organic extract was lost after heat treatment. These results clearly indicate that X. nematophila inhibits PLA2 activity and thereby inhibits eicosanoid biosynthesis, which leads to immunodepression of the infected hosts.

CpxRA Regulates Mutualism and Pathogenesis in Xenorhabdus nematophila

“…volved (directly or indirectly) in maintaining normal cell division and shape, which could influence X. nematophila-host interactions. For example, when injected into the insect blood system, X. nematophila encounters and suppresses insect immunity (29,38,41,(56)(57)(58). If the extended lag phase of the ⌬cpxR1 mutant observed during laboratory growth (Fig.…”

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

“…The bacterium Xenorhabdus nematophila is a pathogen of several insect groups and during infection overcomes insect immunity (3)(4)(5)(6)(7)(8)(9), which is comprised of two central tissues, hemocytes and fat body. Hemocytes include several types of blood cells that mediate cellular responses, such as phagocytosis and aggregation (nodulation) around a microbial invader (10).…”

The bacterium Xenorhabdus nematophila inhibits phospholipases A2 from insect, prokaryote, and vertebrate sources

“…Our preliminary isolation work indicates the presence of two organic soluble factors. These factors inhibit the tobacco hornworm hemocytic PLA2 (Park et al 2004), the hornworm fat-body PLA2, and secretory PLA2s from porcine pancreas, the bacterium S. vilaceoruber, and venoms from the honey bee, A. mellifera, and the spitting cobra, N. mosambica. The X. nematophila factors are inhibitory to PLA2s from a wide phylogenetic range of organisms, including prokaryotes, arthropods, reptiles, and insects.…”

“…In insect systems, bacterial infection stimulates increased hemocytic PLA2 activity (Tunaz et al 2003). We recently learned that factors in X. nematophila culture medium directly inhibit insect hemocytic PLA2 activity (Park et al 2004). PLA2s make up an enzyme superfamily of extraordinarily broad biological significance, including digestion, pathophysiology, phospholipid remodeling, cell signaling, and down-regulating cell signals (for example by hydrolyzing platelet-activating factor; Six and Dennis 2000).…”