Drugs from new sources: Insect microbiome

Why antibiotics are important?

Antibiotics are vital for living a long life. In the past, many people died of generalised infections at a very young age. Complicated surgeries would unlikely bring an excellent prognosis with the high risk of generalised infection due to the absence of effective antibiotics (1).

Antibiotics changed the world and contributed to the increase in life expectancy as, without them, humanity would barely reach its 40's. Besides, many vital surgeries performed nowadays, such as heart and brain surgeries, hip replacement and other orthopaedic and general surgeries, would not be possible without antibiotics. In addition, many people at a young age would likely die of pneumonia and other simple to treat infections like urinary tract infections (1,2).

The Antibiotic Resistance Crisis

Sadly, antibiotics no longer work as they did in the past, and this is due to bacterial resistance to antibiotics. The effect is known as multi-drug resistance. Some scientists predict that the class of antibiotics now available will no longer be effective 50 years later.

To reverse this situation, some scientists had been running a marathon on biodiscovery. Still, unfortunately, their focus is very narrow as their research the same sources of existing antibiotics (3,4). We have a very scarce resource of antibiotics, and this resource primarily consists of derivates of existing antibiotics. However, research precisely based on the same sources of existing antibiotics will take us nowhere. They end up rediscovering known compounds, which are also known by multi-resistant bacteria (4).

Nature can still supply humanity with antibiotics.

Natural soil products are the primary source of known antimicrobials. Most of these antibiotics are produced by Actinobacteria cultured from the soil (3, 4). Streptomyces is the largest genus of Actinobacteria and the source of antibiotics such as streptomycin, chloramphenicol, tetracycline, among others (4). To avoid the rediscovery of antimicrobial compounds known by multi-resistant microorganisms, some scientists changed the focuses from soil cultivated bacteria to alternative microbial sources such as marine microbial environments. Still, these results yielded limited success (3).

Potential novel sources of antibiotics

The insect microbiome is also a source of Actinobacteria, especially Streptomyces, and therefore a potential source for novel antibiotics.

The mechanism that makes insect microbiome a potential source of Streptomyces is that they rely on defensive symbiosis for survival(3). In this type of symbiosis, 'bacterial symbionts produce antimicrobials to protect against opportunistic and specialised microorganisms. For example, Actinobacteria (Streptomyces) in pine beetle (Dendroctonus frontalis) produces the secondary metabolites frontalamide A, frontalamide B, and mycangimycin. Mycangimycin works by inhibiting the beetles' antagonistic fungus Ophiostoma minus and has potent inhibitory activity against malaria, while the frontalamides have general antifungal activity (3)

In vivo studies exploring these new antibiotic compounds on Brazilian Streptomyces isolated from the microbiome of the fungus-growing ant Cyphomyrmex sp resulted in the discovery of a new antibiotic: cyphomycin. The antibiotic cyphomycin worked in mouse with disseminated candidiasis and is active against multidrug-resistant fungal infections both in vitro and in vivo. It is essential to highlight that these in-vivo studies were done in mice only. Still, sadly, this potential source underexplored (3).

A final note

In summary, antibiotic resistance is the new epidemics. It is so severe that even our last resource of broad-spectrum antibiotics is no longer as efficient as in the past (2). There is a great need for new antibiotic research as no new antimicrobial classes have been clinically approved over three decades. Also, nearly 75% of the antimicrobials under clinical development are derived from already known antibiotics and prone to antibiotic resistance (4). Therefore, novel research on novel antimicrobial sources become imperative. Hence, insects are a potential and a rich source for new antimicrobials, and they deserve the attention of the scientific community.

BIBLIOGRAPHY

1. Marianne Frieri, Krishan Kumar, Anthony Boutin. Antibiotic resistance. 2016.

2. de Lima Procópio, Rudi Emerson, da Silva IR, Martins MK, de Azevedo JL, de Araújo JM. Antibiotics produced by Streptomyces. Brazilian Journal of Infectious Diseases. 2012;16(5):466-471. http://dx.doi.org/10.1016/j.bjid.2012.08.014. doi: 10.1016/j.bjid.2012.08.014.

3. Chevrette MG, Carlson CM, Ortega HE, et al. The antimicrobial potential of Streptomyces from insect microbiomes. Nature communications. 2019;10(1):516. https://www.ncbi.nlm.nih.gov/pubmed/30705269. doi: 10.1038/s41467-019-08438-0.

4. Genilloud O. Actinomycetes: Still a source of novel antibiotics. Natural product reports. 2017;34(10):1203-1232. https://www.ncbi.nlm.nih.gov/pubmed/28820533. doi: 10.1039/C7NP00026J.

5. Cheng K, Rong X, Pinto-Tomás AA, Fernández-Villalobos M, Murillo-Cruz C, Huang Y. Population genetic analysis of streptomyces albidoflavus reveals habitat barriers to homologous recombination in the diversification of streptomycetes. Applied and environmental microbiology. 2015;81(3):966-975. https://www.ncbi.nlm.nih.gov/pubmed/25416769. doi: 10.1128/AEM.02925-14.

5. Frei A, Zuegg J, Elliott AG, et al. Metal complexes as a promising source for new antibiotics. Chemical science (Cambridge). 2020;11(10):2627-2639. https://www.ncbi.nlm.nih.gov/pubmed/32206266. doi: 10.1039/C9SC06460E.