Soil is a surprising reservoir of new antibiotics

A Dutch study: soil harbors a huge number of microbes capable of producing effective and as yet unknown antibiotics. Genetic investigation makes it possible to identify them

by Matteo Cavallito

 

Soil microorganisms could be an underestimated source of new antibiotic production. This is reported in a study by the Leiden Institute of Biology in the Netherlands. The research thus highlights new development opportunities for these compounds, which are of particular importance in the face of known problems with pathogen resistance. The search for new antibiotics “has slowed significantly, despite the urgent need for solutions,” a statement says. To date, about 70 percent of these products in use date back to the 1950s, the industry’s decade of greatest expansion that was followed by a long decline in discoveries of new bactericides that continues to this day.

 

Soil bacteria are an untapped resource

“Antibiotic-resistant bacteria pose a major health threat,” the research states. “Addressing this challenge requires among others the development of new antibacterial compounds.” Today many new and potentially more potent antibiotics are still waiting to be discovered, points out Nataliia Machushynets, a biologist and author of the study highlighting the role of microorganisms in producing these compounds that can kill bacteria.

The research focuses “on discovering novel antibiotics from soil bacteria, specifically Streptomyces and Paenibacillus. Despite the vast potential encoded within bacterial genomes, only a fraction of the natural products have been explored experimentally.”

Identifying promising new compounds remains a complex task that requires the use of new and improved techniques. Genomic analysis through DNA sequencing is one of them. Using these tools “made us realise we’ve barely scratched the surface of what bacteria are capable of producing,” Machushynets explains. “Current estimates suggest we know less than 5 percent of their potential.”

Identifying compounds with metabolomics

Currently, the study further points out, “a critical obstacle in antibiotic discovery is the repeated rediscovery of known compounds, a process called replication.” To solve this problem, the researchers adopted a technique called metabolomics, which involves studying the so-called chemical fingerprints of cellular processes. In this way they were able to identify promising compounds in the samples they examined.

Specifically, the techniques used were made available in a platform called nanoRAPIDS, designed, the study further explains, “for the discovery and dereplication of low-abundance bioactive compounds through at-line nanofractionation, molecular networking, and bioactivity assays.” Such a platform “was successfully applied to analyze the bioactive crude extracts of Bacillus and Streptomyces and highlighting the individual mass features that contribute to the activity in the crude extract.”

New frontiers for antibiotics

While advanced spectroscopic techniques, such as metabolomics, have made it possible to detect and characterize antibiotics present in complex bacterial extracts, remember the study, synthetic chemical analysis and bioinformatics have helped researchers discover, optimize and refine the antibacterial properties of compounds. Among the antibiotics identified were tridecaptin, effective against a bacterium known as Pseudomonas aeruginosa and resistant to colistin, and bioactive paenitracin, which acts against vancomycin-resistant Enterococcus faecium.

Other compounds identified included paenylipoeptins, quinazolinones, actinomycin L and tridecaptin lipopeptides, and paenitracin, a new bacitracin variant.

The research, in short, used “a wide range of computational, biological, and analytical chemical approaches to activate cryptic biosynthetic pathways and find new chemistry, thus contributing to the need for new chemical space as the basis for our future antibiotics.” The findings, the study concludes, “highlight that there still is a lot of potential in soil bacteria as sources of novel antibiotics, to aid us in the continuing combat against multi-resistant bacterial infections.”