Immunosuppressive, antimicrobial and insecticidal activities of inhibitor cystine knot peptides produced by teratocytes of the endoparasitoid wasp Cotesia flavipes (Hymenoptera: Braconidae)

Abstract

Teratocytes are specialized cells released by parasitoid wasps into their hosts. They are known for producing regulatory molecules that aid the development of immature parasitoids. We have recently reported the primary structures of cystine-rich peptides, including some containing inhibitor cystine knot (ICK) motifs, produced by teratocytes of the parasitoid Cotesia flavipes (Hymenoptera: Braconidae). ICKs are known for their stability and diverse biological functions. In this study, we produced four putative ICK peptides from the teratocytes of C. flavipes using solid-phase peptide synthesis or recombinant expression in E. coli, and investigated their functions on host immune modulation as well their potential to impair the development of two lepidopterans after ingestion of the peptides. In addition, the peptides were assayed against pathogens and human cells. The peptides did not influence total hemocyte count but suppressed cellular immunity, detectable as a reduction of hemocyte encapsulation (CftICK-I, CftICK-II, CftICK-III) and spread indexes (CftICK-IV) in the host. None of the peptides influenced the activities of prophenoloxidase and phenoloxidase in the hemolymph of larval Diatraea saccharalis (Lepidoptera: Crambidae). CftICK-I and CftICK-II with previously unknown function showed antifungal activity against Candida albicans but were non-toxic to human cells. CftICK-I, CftICK-II, and CftICK-III increased larval mortality and reduced leaf consumption of D. saccharalis, a permissive host for C. flavipes. The CftICK-III also increased larval mortality and reduced leaf consumption of Spodoptera frugiperda (Lepidoptera: Noctuidae), a non-permissive host for C. flavipes. This study highlights biological functions and biotechnological potential of ICK peptides from the teratocytes of C. flavipes.

An Overview of Ovarian Calyx Fluid Proteins of Toxoneuron nigriceps (Viereck) (Hymenoptera: Braconidae): An Integrated Transcriptomic and Proteomic Approach

“…Finally, the study of host-parasitoid interactions by an omic approach, that allows the identification of host regulation factors of parasitic origin, provides useful information and molecules of natural origin that could be used in the biological control of insect pests. Although numerous other studies are necessary, several examples of factors of parasitic that have shown insecticidal activity are reported in the literature [47,61,87] and this could be true also for T. nigriceps OPs.…”

Discovery and Characterization of MaK: A Novel Knottin Antimicrobial Peptide from Monochamus alternatus

“…Knottintype peptides incorporating the ICK motif demonstrate exceptional stability against heat denaturation and protein degradation. These peptides have become valuable assets in disease treatment due to their robustness [22,26,32]. Extensive investigation has revealed that this peptide class effectively displays antimicrobial, antifungal, and antiparasitic properties [32,33].…”

“…This structure is further reinforced by at least three disulfide bonds, resulting in a macrocyclic configuration through pairings like C1-C4, C2-C5, and C3-C6 [22][23][24]. Peptides with this structural configuration exhibit exceptional chemical, thermal, and proteolytic stability, presenting promising prospects for drug development and diagnostic applications [25][26][27]. Notably, their remarkable stability opens novel opportunities for oral drug delivery, unlike other protein therapies, which are typically ill-suited for oral administration due to the distinct conditions of the gastrointestinal tract.…”

Transcriptomic Insights into Host Metabolism and Immunity Changes after Parasitization by Leptopilina myrica

“…Cotesia vestalis injects PDV particles into its hosts, causing apoptosis of host hemocytes and increasing the susceptibility of the hosts to bacterial infections [27]. The teratocytes of C. flavipes produce ICK peptides that suppress the host's cellular immunity [28]. However, comprehensive analyses of how parasitoids manipulate their hosts are largely lacking.…”