Phurealipids, produced by the entomopathogenic bacteria, Photorhabdus, mimic juvenile hormone to suppress insect immunity and immature development

Phurealipids (Photorhabdus urea lipids) are synthesized from Photorhabdus bacteria that are symbiotic to entomopathogenic nematodes. Their chemical structures are similar to that of juvenile hormone (JH) and have been suspected to mimic JH signaling in immunity and the development of insects. This study investigated the physiological roles of phurealipids with respect to their contribution to bacterial pathogenicity using four natural (HB13, HB69, HB416, and HB421) and one derivative (HB27) compound. First, phurealipids like JH suppressed insect immune responses. Overall, phurealipids showed JH like immunosuppressive behavior in a lepidopteran insect Spodoptera exigua larvae. More specifically, phurealipids significantly suppressed the hemocyte spreading behavior which is a key immune response upon immune challenge. Interestingly, the methyl urea derivatives (HB13, HB27, and HB69) were more potent than the unmethylated forms (HB416 and HB421). The inhibitory activity of phurealipids prevented the cellular immune response measured by hemocytic nodule formation in response to the bacterial challenge. Phurealipids also suppressed the expression of cecropin and gallerimycin, which are two highly inducible antimicrobial peptides, in S. exigua upon immune challenge. The immunosuppressive activity of the phurealipids significantly enhanced the bacterial pathogenicity of Bacillus thuringiensis against S. exigua. Second, phurealipids like JH prevented insect metamorphosis. Especially, the methylated urea derivatives of the phurealipids showed the JH-like function by inducing the expression of S. exigua Kr-h1, a transcriptional factor. At the pupal stage, exhibiting the lowest expression of Kr-h1, phurealipid treatments elevated the expression level of Kr-h1 and delayed the pupa-to-adult metamorphosis. These results suggest that phurealipids play crucial roles in Photorhabdus pathogenicity by suppressing host immune defenses and delaying host metamorphosis.