Researchers hunt for tomorrow’s antimicrobial agents in the Christiania topsoil
By Anne Lykke
The world desperately needs new types of antimicrobial agents to combat resistant bacteria. Researchers are therefore searching high and low for new antimicrobial agents—including in a flowerbed in Freetown Christiania in Copenhagen.
Two men sit beside a lush marijuana plant in Christiania, digging in the soil. Suddenly a third man runs towards them shouting: “What are you doing?!” He is clearly upset by the visitors’ proximity to his valuable herb.
“He was fairly angry, but we tried to reassure him that we only wanted a soil sample from the plant’s bed, and that we did it in the name of science,” explains Pep Charusanti, a researcher at DTU Biosustain.
Back home in the laboratory they started investigating the roughly two grams of soil more closely. Soil which may contain substances that can help researchers develop tomorrow’s antimicrobial agents.
Soil bacteria is a gold mine
The reason Pep Charusanti and his colleague Olivier Bitterlin set out for Christiania one September day last year was to collect soil samples and thereby soil bacteria. They had a suspicion that Christiania topsoil in particular might contain interesting bacteria that will help researchers on the hunt for tomorrow’s antimicrobial agents.
“We have sought to collect samples from a wide range of places—such as forests, open fields, gardens, and flower beds. We want to find as many different soil bacteria as possible, so it’s important to collect from different environments,” says Pep Charusanti.
Soil bacteria are extremely interesting to work with in relation to discovering new antimicrobial agents. Seventy per cent of all types of antimicrobial agents used to fight infections today were originally found in soil bacteria. For many years, scientists believed that the reservoir of new antimicrobial agents in soil bacteria had been exhausted, but new methods have shown that soil bacteria can produce far more antimicrobial agents than previously thought.
The method Pep Charusanti and his colleagues use is called ALE (Adapted Laboratory Evolution). In ALE trials, bacteria are ‘trained’ using advanced robots to produce antimicrobial agents.
“The interesting thing is that the bacteria don’t initially produce antimicrobial agents, but if you train them together with pathogenic bacteria, some of them develop the ability to produce antimicrobial agents against their enemies. Using ALE opens up a secret world of antimicrobial agents,” says Pep Charusanti.
Cells to produce antimicrobial agents
The problem of antimicrobial resistance is increasing. Each year, 700,000 people die from resistant infections worldwide. The ‘gram-negative’ group of bacteria has become particularly resistant, and can in many cases no longer be treated using known antimicrobial agents—especially if the patient is already weak. Gram-negative bacteria include those that cause pneumonia, urinary tract infections, blood poisoning, and meningitis (K. pneumoniae, A. baumannii, P. aeruginosa, and E. coli).
The preliminary results of the investigations show that several bacteria from Danish soil can combat pathogenic bacteria.
The next step is to find the chemical combinations of antimicrobial agents the soil bacteria are producing. The researchers are hoping that the antimicrobial agents are new and unknown molecules, and not old acquaintances.
The goal is then to identify the genes responsible for producing the sought after substance. Armed with this knowledge, researchers can genetically modify laboratory bacteria to produce large quantities of the new antimicrobial agent. They can thereby get bacterial cells to serve as microscopic medicine factories, producing the antimicrobial agents of the future.
Hopefully, in a few years we will have some promising new candidates for tomorrow’s antimicrobial agents, found in the Danish soil and mass-produced in microscopic cells.
The soil bacteria from the various sites, including Christiania, were first grown in petri dishes, where colonies of blue, red, and yellow bacteria soon began to flourish.
This image shows how a large soil bacterium is killing the small colonies of pathogenic bacteria on the plate. The soil bacteria colony is releasing an antimicrobial agent that kills bacteria in the immediate vicinity (the transparent area).
Further out—in the milky white area—the pathogenic bacteria are still flourishing, because the soil bacteria’s antimicrobial agents do not reach that far.
source: Technical University of Denmark