Evolution of insect innate immunity through domestication of bacterial toxins

Abstract

Toxin cargo genes are often horizontally transferred by phages between bacterial species and are known to play an important role in the evolution of bacterial pathogenesis. Here, we show how these same genes have been horizontally transferred from phage or bacteria to animals and have resulted in novel adaptations. We discovered that two widespread bacterial genes encoding toxins of animal cells, cytolethal distending toxin subunit B ( cdtB ) and apoptosis-inducing protein of 56 kDa ( aip56) , were captured by insect genomes through horizontal gene transfer from bacteria or phages. To study the function of these genes in insects, we focused on Drosophila ananassae as a model. In the D. ananassae subgroup species, cdtB and aip56 are present as singular ( cdtB ) or fused copies ( cdtB::aip56 ) on the second chromosome. We found that cdtB and aip56 genes and encoded proteins were expressed by immune cells, some proteins were localized to the wasp embryo’s serosa, and their expression increased following parasitoid wasp infection. Species of the ananassae subgroup are highly resistant to parasitoid wasps, and we observed that D. ananassae lines carrying null mutations in cdtB and aip56 toxin genes were more susceptible to parasitoids than the wild type. We conclude that toxin cargo genes were captured by these insects millions of years ago and integrated as novel modules into their innate immune system. These modules now represent components of a heretofore undescribed defense response and are important for resistance to parasitoid wasps. Phage or bacterially derived eukaryotic toxin genes serve as macromutations that can spur the instantaneous evolution of novelty in animals.

Expression pattern analysis of transmembrane receptor TmToll‐8, −9, and −10 in the coleopteran insect Tenebrio molitor following systemic infection

“…The innate immune system of insects plays a significant role in the natural, nonspecific defense mechanisms that protect against pathogens such as bacteria, viruses, fungi, and parasites (Verster et al 2023). Unlike the adaptive immune system found in vertebrates, which develops specific responses to individual pathogens over time, insects rely primarily on innate immune responses to combat infections (Ali Mohammadie Kojour et al 2020; Jang et al 2022).…”

“…Microbe identification via pathways involved in the activation of the proteolytic cascades and the production of antimicrobial peptides (AMPs) are key features of the innate immune response (Sharrock & Sun 2020). In insects, the key components of the innate immune response include the following features: (Verster et al 2023) Physical barriers such as the exoskeleton, which acts as a major physical barrier and blocks pathogen entry inside the body; (Ali Mohammadie Kojour et al 2020) cellular immune response, including activities of diverse immune cells, such as hemocytes, which play a primary role in identifying and eliminating foreign invaders (Walling 2009); (Jang et al 2022) melanization, in which a protective capsule forms around the microbes or foreign invaders to prevent their spread (Nakhleh et al 2017); and (Sharrock & Sun 2020) humoral immune response, including but not limited to AMP production, in which insects synthesize small, cationic peptides that have wide‐spectrum antimicrobial action and are considered fundamental to the innate immune response. These AMPs can directly target or block pathogen growth by disturbing microbe cell membranes (Patyra & Kwiatek 2023).…”

Flies co-opt bacterial toxins for use in defense against parasitoids

“…In PNAS, Verster et al. ( 5 ) explore whether toxins of bacterial origin that have been repeatedly transferred into the genomes of insects function in fruit flies to aid in their defense against parasitoids.…”

“…Some APSE variants encode homologs of a genotoxin called cytolethal distending toxin ( cdtB ) and an apoptosis-inducing protein ( aip56 ) ( 11 – 13 ), both of which also occur in pathogenic bacteria. Amazingly, Vertser and colleagues ( 5 , 14 , 15 ) have found that homologs of one or both toxins have been horizontally transferred into the genomes of insect species spanning at least five orders. The transferred toxins share numerous features with those occurring in APSE phages, including sequence similarity, gene order, and the retention of only the active subunit of cytolethal distending toxin; the binding units (CdtA/CdtC) that facilitate toxin delivery into target cells have been discarded.…”

“…To investigate whether the horizontally transferred toxins actually function in defense against parasitoids, Verster et al. ( 5 ) turned to the fruit fly Drosophila ananassae . Genomic data supported gene duplication and fusion events following toxin acquisition resulting in a single cdtB gene upstream of a pair of hybrid genes each containing cdtB and aip56.…”