Can Insects Counter the Menace of Superbugs

Author: Dr. Dipika Mishra. I hold a Ph.D. degree in Life Sciences from the National Institute of Science Education and Research (NISER) and am a SciCom enthusiast (eLife Community Ambassador for the year 2019-2020). I have composed several scientific poems, some of which have also been featured in the Consilience journal, blogs of GYBN, and the Xylom.

Antibiotics have been always used as a defense to counter myriad bacterial infections and thus have been referred to as miracle drugs. However, the massive and inappropriate use of antibiotics has resulted in bacterial resistance to most of them. This alarming increase in antibiotic-resistant bacteria has led to the loss of numerous lives and has thus reignited the search for new antibiotics. Researchers are toiling to identify new compounds that can serve as antimicrobials. A recent study hints that the solution to this problem lies with arthropods, the members of the jointed appendages family. In two new studies, one on ants (https://doi.org/10.7717/peerj.15645) and the other on fruit flies (https://doi.org/10.1038/s41589-023-01300-x), researchers have identified compounds, secreted from these organisms, that can serve as antimicrobials. These antimicrobials will add to the arsenal of weapons that we have against bacteria.

In dry, arid conditions of the western Australian desert, a unique species of ant thrives. Unlike other typical ants, strangely, this ant species produce honey and are thus referred to as the “Honeypot ants (Camponotus inflatus).” Although, the locals have benefitted from the medicinal properties of this honey, however, no research has been done till date to examine these properties in detail. This recent study aims to unravel the antimicrobial properties of this ant honey.

In yet another interesting study conducted on a fellow arthropod, researchers have identified a compound “Drosocin”. Drosocin is a 19 amino acid long peptide in Drosophila that is rich in cyclic amino acid proline and cationic amino acids, arginine and lysine. This compound is a peptide antibiotic that inhibits bacterial translation termination and thus, protects the fly against microbes. These scientific findings are very significant as they have unraveled the antibiotic activities of compounds secreted from arthropods.

Honeypot Ant Honey (HPAH)

The term “honey” is mostly associated with bees, however, honeypot ants are an exception. This honey is associated with the mulga trees and the aphids that feed on them. Aphids feed on the sugary mulga sap and the honeypot ants in turn coax the aphids to excrete the nectar from their anus and thereby collect the sugary nectar from them. The nectar is then transported by the worker ants to their nests and is then fed to “repletes” i.e., ants that store food for the colony. The abdomen of these replete ants becomes swollen, grape-like, and semi-transparent due to the stored food. These repletes then perform a sacrificial role by becoming immobile and hanging onto the roof of the colony and regurgitating food in times of scarcity. This honey was further analyzed by researchers for its antimicrobial properties.

The researchers observed that in the lab conditions, the honeypot ant honey (HPAH) was extremely effective against the bacterium Staphylococcus aureus. Quite interestingly, S.aureus is resistant to most modern antibiotics. Further, HPAH also inhibited the growth of fungi like Cryptococcus and Aspergillus. Unlike honey secreted by bees which is effective against a wide range of bacteria, HPAH is effective only against specific microbes. Moreover, unlike the peroxide-mediated mechanism of honey bee honey, HPAH operates through a non-peroxide mechanism mediated by other entomological candidates. The non-peroxide components in the honey might include antimicrobial peptides secreted by the ants. This further suggests that HPAH operates through a unique mechanism and its components need to be isolated and studied further.

Drosocin

Most antimicrobial peptides target the bacterial membrane, however, proline-rich antimicrobial peptides penetrate the bacterial cell and target intracellular bacterial components. Proline-rich antimicrobial peptides are further divided into two types, type I which arrest the ribosome at the start codon, and type II which arrest the ribosome at the stop codon. The major function of ribosomes is to synthesize new proteins, these antimicrobial peptides in turn hijack the protein synthesizing machinery of the cell. Until now, apidaecin (Api) from honey bees was the only known type II antimicrobial peptide. However, Drosocin (Dro), found in the genome of fruit flies is the newest recruit in type II proline-rich antimicrobial peptide (PrAMP).

Drosocin inhibits translation termination at the stop codon when the ribosomes reach the stop codon by trapping the RF. Thus, it helps in the self-destruction of the bacterium by targeting the translation machinery. It is effective against both gram-positive as well as gram-negative bacteria. This recent study has identified residues critical for Drosocin’s activity. Although both Dro and Api are members of the type II family, their mechanism of action is slightly different. In the case of Api, only a few C-terminal amino acids are required for its activity, contrastingly, this study identified multiple residues scattered throughout PrAMP for Dro’s activity.

Future Perspectives

The menace of superbugs is haunting researchers worldwide. Bacteria are developing resistance against almost all modern antibiotics. In such a scenario, the presence of antimicrobials in arthropods offers an alternative to antibiotics. By investigating the biochemical properties and the mechanism of action of the honeypot ant honey, researchers can create new antimicrobial compounds. Interestingly, unlike antibiotics, bacteria are susceptible to antimicrobial compounds. Further, by introducing site-directed mutations in Drosocin, its effectiveness as an antimicrobial can be exploited further. Moreover, both these studies also hint at the unexplored domains in the insect kingdom and if carefully studied, it might help us unravel some new mysteries.