Fruit Flies Outsmart Parasitic Wasps by Borrowing Bacterial Armor!

In the ongoing struggle between parasites and their hosts, innovation has been considered essential for a successful offensive or defense that surpasses the rivals.

However, at times, as seen in the corporate arena, outright larceny might serve as a faster method to achieve supremacy.

Biologists at the University of California, Berkeley have revealed that multiple species of fruit flies have appropriated a successful defense mechanism from bacteria to withstand predation by parasitic wasps, which can convert up to half of the fly larvae into makeshift wombs for their offspring -; a gruesome fate that inspired the creature in the 1979 film “Alien.”

Bacteria and other microorganisms are notorious for acquiring genes from other microbes or viruses; this phenomenon, known as horizontal gene transfer, is a key contributor to the concerning antibiotic resistance seen among harmful microbes. Yet, it is believed to occur less frequently in multicellular organisms like insects and humans. An understanding of the prevalence of this process in animals, and how these genes are assimilated and disseminated, can aid researchers in grasping the evolution of animal immune systems and may illuminate pathways for human treatments against parasitic or infectious ailments or even cancer, considered a type of parasite.

“It serves as a framework for understanding the evolution of immune systems, including our own, which also harbors horizontally transferred genes.”

Noah Whiteman, UC Berkeley professor of molecular and cell biology and integrative biology and director of the Essig Museum of Entomology on campus.

In the prior year, the researchers along with their associates in Hungary utilized CRISPR genome editing to disable the gene responsible for the defense mechanism in a prevalent fly species, Drosophila ananassae, discovering that almost all of the genetically altered flies fell victim to predation by parasitic wasps.

In a recent study published on December 20 in the journal Current Biology, the biologists established that this defense -; a gene encoding a toxin -; can be incorporated into the genome of the commonly used laboratory fruit fly, Drosophila melanogaster, rendering them resistant to parasitoid wasps as well. The gene effectively becomes an integral part of the fly’s immune defense, serving as an arsenal to fend off parasites.

The findings demonstrate the vital role of the appropriated defense in the survival of flies and underscore a strategy that could be more commonplace in animals than scientists have presupposed.

“This illustrates that horizontal gene transfer is a significantly underestimated mechanism through which rapid evolution occurs in animals,” remarked UC Berkeley doctoral candidate Rebecca Tarnopol, lead author of the Current Biology paper. “Researchers recognize horizontal gene transfer as a major driver of swift adaptation in microbes, but these occurrences were presumed to be quite rare in animals. However, at least among insects, they appear to be relatively frequent.”

According to Whiteman, the paper’s senior author, “The research indicates that to contend with the relentless stream of parasites that are continually evolving novel tactics to bypass host defenses, an effective strategy for animals is to borrow genes from swiftly evolving viruses and bacteria, and that is precisely what these flies have accomplished.”

Gene transfer from virus to bacteria to fly

Whiteman investigates how insects evolve to counter the toxins produced by plants to prevent predation. In 2023, he released a book titled “Most Delicious Poison,” discussing the plant toxins that humans can enjoy, including caffeine and nicotine.

One plant-herbivore interaction that he examines is between the common fruit fly Scaptomyza flava and sour mustard plants, such as the cresses that flourish in streams around the globe.

“The larvae, which are the juvenile stages of the fly, dwell within the leaves of the plant. They act as leaf miners, creating small trails in the foliage,” Whiteman explained. “They are legitimate parasites of the plant, which tries to eliminate them with its specialized chemicals. We study that evolutionary conflict.”

What he has discovered, however, likely applies to many other insects, which are among the most successful herbivores on the planet.

“These are obscure small flies, yet considering that half of all existing insect species are herbivores, it signifies a highly successful life strategy. Understanding their evolution is crucial for grasping broader evolutionary principles concerning the success of herbivores,” he stated.

Several years ago, while sequencing the fly’s genome in search of genes that confer resistance to mustard toxins, he identified an unusual gene that he discovered to be common among bacteria. Further inspection of previously published genome sequences revealed the same gene present in a related fly, Drosophila ananassae, as well as in a bacterium inhabiting an aphid. Investigations into the aphid revealed a complex narrative: The gene originates from a bacterial virus, or bacteriophage, that infects the bacteria within the aphid. The gene from the bacteriophage, expressed by the bacteria, enables the aphid to withstand a parasitic wasp that threatens it.

These wasps deposit their eggs inside the larvae, or maggots, and remain there until the larvae mature into immobile pupae, at which point the wasp’s eggs develop into larvae that consume the pupae, ultimately emerging as adult wasps.

When Tarnopol initially applied gene editing to express the toxin gene in every cell of D. melanogaster, all the flies perished. However, when she expressed the gene solely in specific immune cells, the fly achieved the same resistance to parasites as its relative, D. ananassae.

Whiteman, Tarnopol, and their team subsequently discovered that the gene located in the D. ananassae genome -; a fusion between two toxin genes, cytolethal distending toxin B (cdtB) and apoptosis inducing protein of 56kDa (aip56), referred to as fusionB -; encodes an enzyme that degrades DNA.

To elucidate how this nuclease can eliminate a wasp egg, the researchers at UC Berkeley collaborated with István Andó at the Institute of Genetics of the HUN-REN Biological Research Centre in Szeged, Hungary, who had previously demonstrated that these same flies possess a cellular defense mechanism against wasp eggs that essentially isolates the eggs from the fly’s body and destroys them. Andó and his laboratory team developed antibodies targeting the toxin, enabling them to monitor its movement throughout the fly’s body, discovering that the nuclease effectively inundates the fly’s system, encircling and obliterating the egg.

“We’ve been uncovering this vast and untapped array of humoral immune factors that could be active in the immune systems of invertebrates,” Tarnopol commented. “Our paper serves as one of the initial examples to demonstrate, at least in Drosophila, that this type of immune response may represent a common mechanism by which natural adversaries like wasps and nematodes are dealt with. They are significantly more lethal in nature than various microbial infections that the majority of individuals.

collaborate with.”

Whiteman and his associates are continuing to investigate the intricacies of the interactions between the fly and the wasp, alongside the cellular and genetic modifications that enabled the flies to produce a toxin without harming themselves.

“If the gene is activated in an inappropriate tissue, the fly will perish. That gene will never proliferate through populations via natural selection,” Whiteman stated. “However, if it resides in a section of the genome close to an enhancer or some regulatory element that triggers its expression slightly in fat body tissue, you can understand how it could gain an advantage very swiftly, resulting in a remarkable benefit.”

The transfer of genes horizontally in any organism could present analogous challenges, he noted, but in the ongoing battle between predator and prey, it may be beneficial.

“When you’re a defenseless little fruit fly, how do you confront these pathogens and parasites that are quickly adapting to exploit you?” he inquired. “One approach is to acquire genes from bacteria and viruses because they rapidly evolve. It’s a clever tactic – rather than waiting for your own genes to assist you, you borrow from other organisms that evolve at a faster rate. And it appears this has occurred multiple times independently among insects, given that many have adopted this gene. It provides us with insight into a new type of dynamism that is present even in creatures that rely solely on innate immune systems without adaptive immunity.”

Whiteman’s research received funding from the National Institute of General Medical Sciences of the National Institutes of Health (R35GM119816). Other co-authors of the publication include Josephine Tamsil, Ji Heon Ha, Kirsten Verster, and Susan Bernstein from UC Berkeley, Gyöngyi Cinege, Edit Ábrahám, Lilla B. Magyar, and Zoltán Lipinszki from Hungary, as well as Bernard Kim from Stanford University.