associations with microbes that provide colonies
with antimicrobial agents."
- C. Nirma, V. Eparvier, D. Stien
Both the mainstream and scientific media frequently report on the urgency of discovering new antibiotics to combat the increasing health threat posed by antibiotic-resistant disease-causing bacteria. The importance of finding new chemical compounds to treat fungal infections gets slightly less attention from the press, but is nevertheless very important. The mid 20th century saw a boom in new antibiotic discovery, but as the century progressed, the usual sources of antibiotics - often bacteria and fungi from soils - appeared to be tapped out. Researchers were growing new strains of bacteria, but kept "re-discovering" old compounds. More recently, it has become evident that one way to discover new compounds is to search for antibiotic-producing bacteria from new and interesting environments. A novel environment ought to provide a unique niche for the bacteria that inhabit it, resulting in the evolution of specialized chemical compounds that serve a role specific to that habitat.
Enter the social insects. Ants, wasps, and termites are three kinds of bugs that live together in large numbers within colonies of their own construction. Just like human societies, different members play different roles, all working for the betterment of the community (OK, maybe not totally like human society...). And also just like humans, the social insects have to be able to deal with the occasional infectious disease outbreak, with the major difference being that there are no members of their community specialized to write prescriptions or administer drugs. Instead, the insects outsource the work of drug development and production to some powerful microbial allies. Thus emerges a beautiful and fascinating mutualistic symbiosis - a mutually beneficial relationship between different species of living things - wherein the insects provide the microbes with a home and food and the microbes produce antibiotic or antifungal compounds to protect the insects from infection. Essentially, the microbes play the role of the pharmaceutical chemist in the insect society. This has previously been seen with ant and wasp colonies, for example. Currently available as an advanced online publication in the Journal of Natural Products, C. Nirma, V. Eparvier and D. Stien report the discovery of N-methyltyroscherin from a fungus named Pseudoallescheria boydii that was isolated from a colony of the Amazonian termite Nasutitermes sp. A slightly different version of the compound, called tyroscherin, had previously been discovered by Watanabe and coworkers by virtue of its toxicity towards breast cancer cells.
The structure was determined using normal Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) based techniques. The N-methyl group was assigned via chemical methylation of tyroscherin using methyl iodide. Although the de-methyl analog of the compound (lacking a CH3 group on the N atom) was already known (Watanabe ref. above), what is most fortuitous about this study is that N-methyltyroscherin was isolated based on its ability to kill disease causing fungi. Thus, although this may seem on the surface to harken back to our theme of "molecular re-discovery", a new and potentially useful function - antifungal activity - was revealed. The termites would likely agree that the fungus-killing activity of N-methyltyroscherin is useful. Perhaps more importantly, this study reveals yet again that the microbial members of social insect communities are likely to be a unique and useful source of chemical compounds that could help treat important infections, whether you are a human or a bug.
- @EJDimise
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