Looking for next-generation antibiotics from trash-heap insects

Environment and sustainability 11. jun 2024 4 min Senior Scientist Chrysantus M. Tanga, PhD Cynthia M. Mudalungu Written by Eliza Brown

New research reveals that chemicals from a common fly might combat harmful bacteria such as Escherichia coli and Staphylococcus aureus, offering hope against the global crisis of antibiotic resistance. Since overusing antibiotics causes bacteria to evolve rapidly, innovative solutions are urgent. This research highlights how fly larvae, found in decomposing plant matter, produce unique antimicrobial agents. Scientists have identified potential new compounds, emphasising the need to further explore natural resources in our fight against superbugs.

A recent study, published in ACS Omega, suggests that chemicals created by a humble fly could be effective against strains of E. coli and S. aureus.

Antimicrobial resistance is a worldwide crisis. After decades of prescribing excessive antibiotics, bacteria have evolved to circumvent antibiotics faster than we thought possible. According to the World Health Organization, antibiotic-resistant bacteria directly caused more than 1.2 million deaths in 2019 and contributed to a further 5 million deaths.

Experts say that overcoming these superbugs will require antimicrobial agents with totally new modes of action, ways to attack and undermine bacteria that differ radically from existing antibiotics.

The answers may be closer to home than we realise – perhaps even in your own backyard. Researchers at the International Centre of Insect Physiology and Ecology in Nairobi, Kenya are looking for clues from the black soldier fly, a decomposer that lives on rotting plant matter.

Looking for next-generation antibiotics from a trash-heap insect is a remarkable opportunity to “go beyond the value of waste to create therapeutic agents that could be very useful for humanity,” says co-author Chrysantus Tanga, an agricultural entomologist at the Centre.

A fly with a secret superpower

Shiny black bugs that resemble wasps, black soldier flies have expanded their range to include almost the whole world, from Australia and Africa to Europe and the Americas. They are likely in your area now, their plump larvae munching on cast-off plant matter or other waste.

But put down the bug swatter – as far as flies go, they are very polite neighbours.

Black soldier flies are not attracted to human food like their distant cousin, the housefly, and since they are very ineffective at flying, you could start a colony in your backyard compost pile without worrying that they will infest your home, Chrysantus Tanga explains.

In Kenya, black soldier fly larvae have emerged as a popular animal feed – they are easy to rear, require waste as the only input and are high in protein. But what farmers may not realise is that the larvae are also immune endurance champs, outlasting the slurry of bacteria, viruses and microbes in their trash-heap homes.

As soon as they hatch, black soldier fly larvae “have to be their own doctors by coming up with defensive mechanisms that will enable them to survive,” Chrysantus Tanga says. “You can imagine the quantity of pathogens you get in decomposed material.”

How to activate a fly’s immune system

Producing antimicrobial compounds requires considerable investment of energy and resources, so the larvae likely calibrate their response to the threats they face. As such, the researchers suspected that the choice of waste material on which the larvae were raised might cause them to amplify or relax their microbial defences.

Lead author and PhD student Mach Achuoth reared larvae on four materials or substrates – pig manure, rabbit manure, potato waste and market waste. Market waste is “the leftovers of agricultural products, fruits and vegetables that cannot be sold and would otherwise be dumped somewhere,” explains co-author Cynthia Mudalungu, a natural products chemist.

Once the larvae reached their fifth instar (developmental stage), the researchers scooped them up, dried them in an oven and then ground their bodies in a blender. Then, they used a variety of solvents to draw out various chemicals from the resulting sludge. Liquid hexane was used to extract oily components such as fatty acids, shown to have antimicrobial properties in previous studies. But the researchers were interested in what other chemical weapons the larvae had in their arsenal – so they also prepared extracts using methanol and acetic acid, which would bring out compounds with different chemical properties.

Those liquid extracts were then placed in petri dishes with strains of four pathogens: S. aureus, which causes one of the top five hospital-acquired infections; E. coli, a contaminant in food and drinking-water spread by faeces; Pseudomonas aeruginosa, which can infect the blood and lungs and is frequently contracted by hospital patients after surgery; and Bacillus subtilis, a bacteria found in the human gut that rarely triggers infections.

Would the material the larvae fed on and lived in affect the potency of their antimicrobial effect?

Plant power

It was immediately clear that the larvae did not fare well overall in the animal manure. At harvesting time, the plant materials yielded about 4 kg of larvae each, whereas just 1.0–1.5 kg of larvae were gathered from the manure.

But across the board, larvae reared on plant matter packed a bigger antimicrobial punch, Cynthia Mudalungu says. The reason may be the nutritional composition of the substrates themselves: plant waste is high in carbohydrate, an important source of energy, which may give the larvae more resources to invest in a strong immune response.

Although previous studies had identified antimicrobial properties in the oily components of the liquid extract, “in our study we found that the activity is also in the acetic acid extract,” Cynthia Mudalungu explains.

“That tells us that, in addition to the identified fatty acids, we must also aim to find out what other bioactive compounds there are in these extracts,” she adds.

Of the various extract–bacteria matchups, the most impressive result was the acetic acid extract from market waste. Flushing the larvae sludge with acetic acid likely drew out peptides and polypeptides, an important component of the immune response for everything from microorganisms to humans. Peptides often work by burrowing holes in a bacteria’s cell membrane until they die or forcing bacteria to spread out, preventing them from communicating and multiplying.

What is next?

The researchers say that their study is an important lesson for the myriad other teams working to find the next antimicrobial therapy in insects: rearing an insect in the wrong environment can fail to fully activate its immune system, causing researchers to miss potential therapeutic agents.

Insects are a “major source of natural compounds” that should not be ignored, Chrysantus Tanga emphasises. “In terms of accessibility, availability and year-round supply, this product can be more efficient for most of the sources of antibiotic compounds that are actually being used currently.”

Cynthia Mudalungu says that the team is already hard at work isolating and identifying compounds from the acetic acid extracts. From there, they will get back to the petri dishes to determine which are the best candidates for drug development. This experiment tested the larval extracts against bacterial strains that respond well to antibiotics, so future experiments will put the compounds through their paces with antibiotic-resistant bacteria.

“We believe that the compounds we will get may be superior to the ones that already exist,” Cynthia Mudalungu says.

Unlocking the potential of substrate quality for the enhanced antibacterial activity of black soldier fly against pathogens” has been published in ACS Omega. The research was funded by the Australian Centre for International Agricultural Research, the Norwegian Agency for Development Cooperation, the Rockefeller Foundation, the Bill & Melinda Gates Foundation, Horizon Europe, the Curt Bergfors Foundation Food Planet Prize Award, and the Novo Nordisk Foundation.

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