Microbes have long been engaged in warfare; these cells have to find a place to survive and thrive, and collect enough nutrients to function and grow. Many microbes, therefore, produce compounds that can kill other microbes. For example, there are also viruses known as bacteriophages that only infect bacterial cells, and can destroy those cells; there are also many bacteria that generate bacteria-killing antibiotics,
But bacteria can easily evolve resistance to drugs and share that with other bacterial cells. Antibiotic-resistant bacterial infections are a growing problem that is only expected to get much larger. Scientists have been searching for new antibiotics for many years. It’s challenging to develop these medications, and scientists have found some success by looking to compounds generated by bacteria.
But some bacteria are very hard to grow in the lab. In new research reported in Nature Biotechnology, scientists bypassed the bacterial culture problem, and simply collected a bunch of soil, then applied advanced genetic techniques.
They were able to collect large fragments of high-quality microbial DNA fragments right from the soil samples. Then they used long-read nanopore sequencing to analyze sequences that were tens of thousands of base pairs long, this is about 200 times longer than previous tools, which often involve chopping DNA into small bits, and then reassembling the sequences. Since bacterial genomes are already small and soil contains huge numbers of bacterial genomes, this novel approach allowed the researchers to get better results. They could look at whole bacterial genomes in a new way that revealed the genetic sequences for many different biomolecules.
With this trove of novel bacterial genetic data, and cutting edge technologies to sequence and analyze it, the investigators found two potential new antibiotics. While much more work will be necessary to show that these compounds are safe and effective, the work shows how we can take advantage of resources that are readily available to develop novel drugs.
"We finally have the technology to see the microbial world that have been previously inaccessible to humans, and we're not just seeing this information; we're already turning it into potentially useful antibiotics. This is just the tip of the spear" noted corresponding study author Sean F. Brady, head of the Laboratory of Genetically Encoded Small Molecules at Rockefeller.
"We're mainly interested in small molecules as therapeutics, but there are applications beyond medicine," added first study author and postdoctoral researcher Jan Burian. "Studying culturable bacteria led to advances that helped shape the modern world and finally seeing and accessing the uncultured majority will drive a new generation of discovery."
AI is also being applied to the problem. Not only have computational tools been used to sift through vast numbers of drug candidates to identify the best potential antibiotics, researchers have also shown that generative AI can be used to design antibiotics.
Sources: Rockefeller University, Nature Biotechnology
