MIT biologists have provoked soil-dwelling bacteria into producing a new type of antibiotic by pitting them against another strain of bacteria in a battle for survival.
The antibiotic holds promise for treatment of Helicobacter pylori, which causes stomach ulcers in humans. Also, figuring out the still murky explanation for how the new antibiotic was produced could help scientists develop strategies for finding other new antibiotics.
The work is reported in the February issue of the Journal of the American Chemical Society.
A combination of luck, patience and good detective work contributed to the discovery of the new antibiotic, according to Philip Lessard, research scientist in Professor Anthony Sinskey's laboratory at MIT.
Sinskey's lab has been studying Rhodococcus, a type of soil-dwelling bacteria, for many years. While sequencing the genome of one Rhodococcus species, the researchers noticed that a large number of genes seemed to code for secondary metabolic products, which are compounds such as antibiotics, toxins and pigments.
However, Rhodococcus does not normally produce antibiotics. Many bacteria have genes for antibiotics that are only activated when the bacteria are threatened in some way, so the researchers suspected that might be true of Rhodococcus.
Kazuhiko Kurosawa, a postdoctoral associate in the Department of Biology, decided to try to provoke the bacteria into synthesizing antibiotics by placing them in stressful environments. He tried turning the temperature up and down, then altered the bacteria's growth medium, but nothing worked.
Kurosawa then decided to stress the Rhodococcus bacteria by forcing them to grow in the presence of a competing bacteria, a strain of Streptomyces. Streptomyces produces an antibiotic that normally kills other bacteria, but in one of the experimental test tubes, Rhodococcus started producing its own antibiotic, which wiped out the Streptomyces.
The researchers isolated the antibiotic, dubbed it rhodostreptomycin, and started testing it to see what else it would kill. It proved effective against many other strains of bacteria, most notably Helicobacter pylori. Rhodostreptomycin is a promising candidate to treat H. pylori because it can survive in very acidic environments such as the stomach.
The antibiotic turned out to be a type of molecule called an aminoglycoside, composed of peculiar sugars, one of which has a ring structure that has not been seen before. The ring structure could offer chemists a new target for modification, allowing them to synthesize antibiotics that are more effective and/or stable.
"Even if (rhodostreptomycin) is not the best antibiotic, it provides new structures to make chemical derivatives of," said Lessard. "This may be a starting point for new antibiotics."
One mystery still to be solved is why Rhodococcus started producing this antibiotic. One theory is that the presence of the competing strain of bacteria caused Rhodococcus to "raise the alarm" and turn on new genes.
The version of Rhodococcus that produces the antibiotic has a "megaplasmid," or large segment of extra DNA, that it received from Streptomyces. A logical conclusion is that the plasmid carries the gene for rhodostreptomycin, but the researchers have sequenced more than half of the plasmid and found no genes that correlate to the antibiotic.
Another theory is that the plasmid itself served as the "insult" that provoked Rhodococcus into producing the antibiotic. Alternatively, it is possible that some kind of interaction of the two bacterial genomes produced the new antibiotic.
"Somehow the genes in the megaplasmid combined with the genes in Rhodococcus and together they produced something that neither parent could make alone," said Lessard.
If scientists could figure out how that happens, they could start to manipulate bacterial genomes in a more methodical fashion to design new antibiotics.
Other authors of the paper are T.G. Sambandan, research scientist in MIT's Department of Biology, MIT professors Anthony Sinskey of biology and ChoKyun Rha of the Biomaterials Science and Engineering Laboratory, and Ion Ghiviriga and Joanna Barbara of the University of Florida.
The research was funded by the Cambridge-MIT Institute and the Malaysia-MIT Biotechnology Partnership Program.
Written by Anne Trafton, MIT News Office
Elizabeth A. Thomson | MIT News Office
Turning carbon dioxide into liquid fuel
06.08.2020 | DOE/Argonne National Laboratory
Tellurium makes the difference
06.08.2020 | Friedrich-Schiller-Universität Jena
Scientists at the Fraunhofer Institute for Laser Technology ILT have come up with a striking new addition to contact stamping technologies in the ERDF research project ScanCut. In collaboration with industry partners from North Rhine-Westphalia, the Aachen-based team of researchers developed a hybrid manufacturing process for the laser cutting of thin-walled metal strips. This new process makes it possible to fabricate even the tiniest details of contact parts in an eco-friendly, high-precision and efficient manner.
Plug connectors are tiny and, at first glance, unremarkable – yet modern vehicles would be unable to function without them. Several thousand plug connectors...
An international research team has found a new approach that may be able to reduce bone loss in osteoporosis and maintain bone health.
Osteoporosis is the most common age-related bone disease which affects hundreds of millions of individuals worldwide. It is estimated that one in three women...
Traditional single-cell sequencing methods help to reveal insights about cellular differences and functions - but they do this with static snapshots only...
“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.
Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...
An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.
Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...
23.07.2020 | Event News
21.07.2020 | Event News
07.07.2020 | Event News
06.08.2020 | Earth Sciences
06.08.2020 | Power and Electrical Engineering
06.08.2020 | Life Sciences