[Editors] Bacterial 'battle for survival' leads to new antibiotic

[Elizabeth Thomson]

MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA  02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

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Bacterial 'battle for survival' leads to new antibiotic

-- Holds promise for treating stomach ulcers
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For Immediate Release
TUESDAY, FEB. 26, 2008
Contact: Elizabeth A. Thomson, MIT News Office -- Phone: 617-258-5402 
-- Email: thomson at mit.edu

PHOTO AVAILABLE

CAMBRIDGE, Mass.--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.

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Written by Anne Trafton, MIT News Office