‘David and Goliath’: A tale from the microbial world

Actinobacteria demonstrate how size does not always mean might

Photo by James Pond on Unsplash

If you’ve ever had the unfortunate experience of stepping on lego in bare feet, you know the truth: in life, size does not always win.

Outside of the domestic world, there are a plethora of examples where this is true, from the infamous ‘black widow’ spider to the less well known, but disgustingly impressive, single-celled Hastigerinella digitata.

In this post, let’s take a peek at a really small example — the microscopic strain of bacteria (WAC-288) from the phylum actinomycetes. Species from this phylum are found everywhere: in the soil, on the skin, even in our guts. Although some species are pathogenic, many species of actinomycetes are commensal organisms, so in general, we and other creatures live pretty happily alongside them (1).

Actinomycetes are known to produce a vast array of compounds, many of which have been shown to have pharmaceutical applications (2).

Scanning electron micrograph of Actinomyces israelii (false colour). GrahamColm at English Wikipedia, CC BY 3.0, via Wikimedia Commons

However, certain members of the ubiquitous and useful actinobacteria have been shown to have a rather dark side…

… particularly if you are a fruit fly.

Up until recently, all the examples of relationships between actinomycetes and insects were of benefit to the insect (3). For example, female members of the solitary ‘Beewolf’ wasp species coat their young in bacteria to protect them from fungal colonisation (4).

Researchers Ho et al., based in Toronto, Canada, have pinpointed particular gene clusters in members of the actinomycetes that act to attract fruit flies, encouraging them to lay their eggs, and then, by producing a deadly poison, destroy the larvae (3).

Actinomycetes: the ‘venus-fly trap’ of the microbial world?

Photo by Jeffery Wong on Unsplash

Different species of actinomycetes produce different toxins. In their paper, the authors focus on the gene cluster present in the WAC-288 strain. This gene cluster codes for the compound 2-Methylisoborneol (2-MIB), which acts as a chemical attractant (3, 5), and the compound cosmomycin-D which kills the fruit fly larvae.

2-MIB is a class of terpene. Terpenes are volatile hydrocarbons produced by many plants. They have a range of structures but many are associated with particular fragrances (6). 2-MIB is well known for it’s characteristic ‘musty’ or ‘earthy’ smell — in fact, it is frequently cited as the biological agent behind tainted drinking water (7).

Chemical structure of 2-methylisoborneol, Edgar181, Public domain, via Wikimedia Commons

Cosmomycin-D is a type of anthracycline (8). Anthracyclines are often used as chemotherapeutic agents thanks to their ability to interfere with DNA replication. Cosmomycin-D has been shown to bind to DNA (9) and interfere with RNA transcription (10) thereby killing the cell. It was found that Cosomycin D killed the fruit-fly larvae by inducing the death of cells in their digestive system (3).

Synthesising secondary metabolites such as Cosmomycin-D and 2-MIB takes up valuable energy and resources. So from an evolutionary perspective, it is likely that these metabolites play key biological roles.

Here’s where things become less clear: does the ability to attract and then kill fruitflies somehow benefit the bacteria? My favourite suggestion is that species of actinomycetes might metabolise the dead larvae — utilising them as a food source… (3).

…Very venus-fly trap.

Elsewhere in their paper, the authors make a suggestion from another perspective: perhaps this risky relationship actually benefits the fruit fly? Could the bacteria be protecting the insect’s food source from other predators (3)?

Given that other species of actinobacteria have similar ‘attract-and-kill’ gene clusters, the authors suppose that this type of lethal-relationship is potentially widespread. Indeed, if we take a broader view, we find that the natural world is filled with examples of complex, risky relationships between organisms of different species.

In the picture below, we see the Caribbean broadstripe goby fish is contrasted by vivid orange coral. This species is an example of a ‘cleaner fish’ or Doctor fish and are found in the Caribbean and West Atlantic oceans (11).

The ‘cleaning activity’ of this fish is another example of a risky relationship: the goby, when cleaning other fish, utilises the cleaned detritus as a food source. However, as the ‘client fish’ are often suffering from infections by parasites such as viruses, parasites and bacteria, the goby risks becoming infected themselves, or worse, being eaten by their clients (12).

Broadstripe Goby fish. Image source: Smithsonian Tropical Research Institute, 2015.

There are two broadstripe goby ecotypes: those that live in coral and act as cleaners and those that live on sponges that do not. The sponge-dwelling, non-cleaning gobies have been shown to grow faster and have higher survival rates (12). Yet, the population of cleaner goby fish persists in evolution — despite their ‘fast and loose’ lifestyle.

For me, this is what fascinates me about the natural world: we can examine it, take each part and observe what it does but understanding how everything fits as a whole and why things are as they are is another matter entirely…

References

1. The Editors of Encyclopaedia Britannica, Actinomycetes. Encyclopædia Britannica. Published: November 21, 2018. https://www.britannica.com/science/actinomycete
2. Jakubiec-Krzesniak K, Rajnisz-Mateusiak A, Guspiel A, Ziemska J, Solecka J. Secondary Metabolites of Actinomycetes and their Antibacterial, Antifungal and Antiviral Properties. Pol J Microbiol 3, 67 (2018). doi:10.21307/pjm-2018–048
3. Ho LK, Daniel-Ivad M, Jeedigunta SP et al. Chemical entrapment and killing of insects by bacteria. Nat Commun 11, 4608 (2020). https://doi.org/10.1038/s41467-020-18462-0
4. Kaltenpoth M, Göttler W, Herzner G, Strohm E,
   Symbiotic Bacteria Protect Wasp Larvae from Fungal Infestation. Current Biology 15, 5 (2005). https://doi.org/10.1016/j.cub.2004.12.084.
5. Becher PG, Verschut V, Bibb MJ. et al. Developmentally regulated volatiles geosmin and 2-methylisoborneol attract a soil arthropod to Streptomyces bacteria promoting spore dispersal. Nat Microbiol 5, 821–829 (2020). https://doi.org/10.1038/s41564-020-0697-x
6. Omar J, Olivares M, Alonso I, Vallejo A, Aizpurua‐Olaizola O. and Etxebarria N. Quantitative Analysis of Bioactive Compounds from Aromatic Plants by Means of Dynamic Headspace Extraction and Multiple Headspace Extraction‐Gas Chromatography‐Mass Spectrometry. Journal of Food Science 81 C867-C873 (2016). https://doi.org/10.1111/1750-3841.13257
7. Jüttner F, Watson SB. Biochemical and Ecological Control of Geosmin and 2-Methylisoborneol in Source Waters. Applied and Environmental Microbiology 14, 73 (2007). DOI: 10.1128/AEM.02250–06
8. Ando T, Hirayama K, Takahashi R, Horino I, Etoh Y, Morioka H, Shibai H & Murai A. Cosmomycin D, a New Anthracycline Antibiotic. Agricultural and Biological Chemistry 49, 1 (1985) DOI:10.1080/00021369.1985.10866713
9. Kelso C, Tillott V, Rojas JD, Furlan RLA, Padilla G, Beck JL.
   Mass spectrometric investigation of the DNA-binding properties of an anthracycline with two trisaccharide chains. Archives of Biochemistry and Biophysics 477, 2 (2008) https://doi.org/10.1016/j.abb.2008.05.009.
10. Kelso C. Investigation of the DNA-binding properties of cosmomycin D, an uncommon anthracycline compound. Doctor of Philosophy thesis, School of Chemistry, University of Wollongong. (2010) https://ro.uow.edu.au/theses/3971
11. Smithsonian Tropical Research Institute. Species: Elacatinus prochilos, Broadstripe goby. Published: 2015 https://biogeodb.stri.si.edu/caribbean/en/thefishes/species/4151
12. Xavier R, Mazzei R, Pérez-Losada M, Rosado D, Santos JL, Veríssimo A, Soares MC. A Risky Business? Habitat and Social Behavior Impact Skin and Gut Microbiomes in Caribbean Cleaning Gobies. Frontiers in Microbiology 10, (2019) DOI=10.3389/fmicb.2019.00716