In the 60s, more than 10 antibiotics were discovered. In the 70s, this number raised up to 17. It kept surging until hitting its peak in the 80s, when we found 41 antibiotics we didn’t know before. From then, it has been a steady decline. In the last ten years, we have come across only 7 new compounds. We are far from the golden days, and it is not a trivial matter: as antibiotic resistance spreads, we need new weapons to keep the infections at bay.
Lately, a new type of molecule has been the focus of researchers worldwide: RiPPs. RiPPs (the acronym for Ribosomally synthesized and post-translationally modified peptides) are compounds produced naturally by different types of organisms like archaea, prokaryotes and eukaryotes. Many show great potential, making them excellent candidates for future drugs. Identifying the right samples is relatively easy: they are the ones impeding bacterial growth. But knowing the molecular instructions (DNA sequences) that the organisms use to produce the RiPP in the sample, to reproduce them later, is no easy task.
Scientists start with the samples extracted from the environment (seawater, animals’ guts or soil, for example). They contain a lot of DNA, which makes it extremely difficult for researchers to identify which parts of the whole sample are responsible for producing the RiPP molecule. It’s a sort of needle-in-the-haystack situation.
To help fellow researchers in this process, our colleagues at the University of Groningen created BAGEL back in 2006. It is a website service that enables researchers to enter the DNA sequence of their sample and, with a simple click, compare it against a library of almost 500 RiPPs sequences. As a result, the researcher obtains a detailed report showing the areas of interest in their DNA sample.
Now, is in its fourth version: BAGEL4 and, thanks to the last update, is able to give more information about the DNA sequence. It can even predict promoters and terminators of the area of interest: the sequence of letters within the DNA sample that mark the beginning and the end of the region of DNA that contains the information to produce a RiPP. This could help geneticists isolate this region from the sample, accelerating the process of incorporating it into other microorganisms, so they can produce RiPP in industrial amounts.
What may seem a small advance could have a positive impact in the day to day of many antibiotic researchers. The path from a promising sample until a new antibiotic hits the shelves at the pharmacy is a long one. For each new drug that makes it to the market, between 5000 and 10000 compounds are discarded. So, speeding up the process of mining the interesting sequence, to check each candidate faster, is crucial. Computer power is now at its peak, and tools like BAGEL4 make this hasty process much easier. And, in the end, we all benefit from having better, faster tools in the fight against bacterial resistance.