Scientists have provoked a soil-dwelling bacteria into producing a potent antibiotic by pitting it against another bacteria, despite the fact that previously it had never been known to produce such products.
The mechanism behind the phenomena is still a mystery, but once this is better understood scientists hope to learn how to manipulate other bacteria to produce previously unknown pharmaceutical products.
The researchers first noticed that the Rhodococcus bacteria may have hidden properties when they were sequencing its genome. By comparing its DNA with the genome of other bacteria, the researchers noticed that the Rhodococcus shared many genes that are known to contribute to the production of antibiotic chemicals.
"By far the best studied source of antibiotics comes from Streptomyces bacteria," Phillip Lessard, a member of the research team, told LabTechnologist.com. "However, compared to Streptomyces the number of genes [devoted to antibiotic production] in Rhodococcus is far greater. It looks like Rhodococcus has an arsenal that is loaded to make antibiotics."
The team, lead by Kazuhiko Kurosawa, knew that genes are sometimes only expressed under adverse situations, so they tried to place the bacteria under environmental strain to see if they could force it into producing an antibiotic. Attempts at changing the ambient temperature and the nutrient supply produced little effect, but eventually the team decided to grow the bacteria in direct competition with a hardy strain of the Streptomycese bacteria
This bacteria itself produces a very potent antibiotic that the researchers considered likely to kill the Rhodococcus. "We thought that if anything will stress the Rhodococcus cells, this will," said Lessard.
However, rather than surrendering to the Streptomyces, the Rhodococcus managed to kill all of the competition inside the test tube. The team then isolated the antibiotic, dubbed rhodostreptomycin, and tested it on other types of bacteria - many of which it successfully killed.
If the drug passes clinical tests researchers believe that the antibiotic may be particularly useful to fight against Helicobacter pylori, as it can withstand the highly acidic conditions of the stomach. The rhodostreptomycin molecule may also be useful as a pharmaceutical building block for other products, as it features an interesting two-ring structure that has not been seen in previous antibiotics.
"Even if it is not the best antibiotic, it provides new structures to make chemical derivatives," said Lessard. "This may be a starting point for new antibiotics."
The mechanism behind the production of rhodostreptomycin is still not fully understood. The mystery lies in the fact that the Rhodococcus genome did not appear to contain the right genes to produce the rhodostreptomycin antibiotic. Rhodostreptomycin is an amino glyceride antibiotic, but the Rhodococcus genome appeared better suited to producing two other classes of antibiotics - PKS and NRPS.
It's possible that the "knowledge" of how to produce the antibiotic did not come from the Rhodococcus genome at all. The cells of Rhodococcus bacteria grown with the Streptomycese contain a megaplasmid that contains some "borrowed" DNA from its competitor. While it is possible that the ability to produce the antibiotic comes solely from this DNA or from its own DNA, the team believe that the ability may come from a combination of the two.
"The exciting possibility is that by combining information from two organisms you are not limited to what the individual species knew how to do," said Lessard. "A given host can be used to produce a range of compounds not all of which it knew how to do in the first place."