A new method for discovering antibiotics makes use of an unusual source of complex microbial communities
Roisin McGuigan |
A team of scientists has developed a technology that rapidly assesses antibiotics using microbes from a curious source: saliva taken from the East Siberian brown bear. We spoke to co-author of the associated paper (1), Konstantin Severinov, a professor based in the Waksman Institute of Microbiology at Rutgers University, to discuss antibiotic screening – and how to catch a drooling bear…
Why use bear saliva?
We are part of a long-term expedition to Kamchatka, so a bear was a natural choice – bears have a diverse diet, so we assumed that their microbiome will also be diverse. They also have lots of drool! The challenge, of course, was to catch one. A trained hunting husky was used to lure a bear into a cage. Once inside, it was offered a stick covered with absorbent canvas, which it duly bit, and there was plenty of saliva to pack into test tubes once it let go. It did get some honey as a consolation prize, and was released again with the help of the husky.
How does the method work?
Current procedures for screening microbes for antibiotic production are tedious and require testing individual isolates one by one. The power of our procedure is that microbes from various communities (in our case, the oral cavity of a wild bear) are cultivated in oil drops filled with nutritious medium, where they are isolated from each other and cannot affect each other’s growth. In the presence of a target microbe – in our case, Staph aureus, which had been made fluorescent with a green protein – we can detect the effect of these droplet-incarcerated microbes on growth.
We can sort the droplets at tens of thousands per minute using fluorescence activated sorting to isolate droplets (and the microbes contained in them) with lower florescence, where Staph growth is inhibited, presumably because of some noxious compound produced by the microbe. Our method still depends on cultivation, which is a major limitation, as most microbes are not easily cultivated in the lab.
What impact does the method have on the discovery of new antibiotics?
The throughput of our procedure should allow scientists to screen orders of magnitude more microbiota cells, and hopefully find new antibiotic producers. Once identified with our procedure, there will be the “normal” workflow of identifying the compound, determining its structure, genes responsible for its synthesis, spectrum of antibacterial action, and so on.
We also think that the procedure could easily be applied to rapidly determine the susceptibility of microbes in a community to a particular drug – we describe this in more detail in our paper (1): you essentially load droplets with microbes, nutritious medium, and various concentrations of an antibiotic or a control. For strains that are susceptible to the antibiotic you test, you will see depletion in representation after growth.
Next, we plan to apply our procedure to microbiota from other microbial communities – both “exotic”, such as a Komodo dragon, and “standard” (human), to hopefully find new antibiotic leads.
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- SS Terekhov et al., “Ultrahigh-throughput functional profiling of microbiota communities”, Proc Natl Acad Sci USA, 115, 9551–9556 (2018). DOI: 10.1073/pnas.1811250115.