Scientists Hot on Trail of New Antibiotics

FRIDAY Oct. 17, 2008 -- Researchers believe they are close to perfecting a new class of broad-spectrum antibiotics that could counter increasingly drug-resistant bacteria, a new study says.

The new antibiotics compounds -- all of which are natural products produced by certain bacteria to battle other bacteria -- also show promise as a more effective and faster treatment for tuberculosis. One in three people worldwide carries TB, and today's antibiotics are not efficient in combating it.

The new research, published in the Oct. 17 issue of the journal Cell, is encouraging, because bacterial infectious diseases are responsible for a quarter of all deaths worldwide. For all major bacterial pathogens, strains resistant to at least one current antibiotic have arisen, according to one researcher.

"For six decades, antibiotics have been our bulwark against bacterial infectious diseases," Richard Ebright, a Howard Hughes Institute investigator at Rutgers University, said in an interview issued by the journal's publisher. "Now, this bulwark is collapsing. There is an urgent need for new antibiotic compounds and practical new targets."

The new antibiotic compounds under study are myxopyronin, corallopyronin, and ripostatin. They block the action in bacteria of RNA polymerase, an essential protein in all organisms that is necessary to transcribe the genetic instructions in DNA into RNA, which in turn directs the assembly of proteins.

"RNA polymerase has a shape reminiscent of a crab claw, with two prominent pincer-like projections," Ebright said. "Just as with a real crab claw, one pincer stays fixed and one pincer moves, opening and closing to keep DNA in place. The pincer that moves does so by rotating about a hinge. Our studies show that the three antibiotics bind to and jam this hinge."

"It's an amazing site," Eddy Arnold, also of Rutgers University, said of this hinge that the researchers refer to as a switch region. "It's a drug designer's dream, because it's a pocket that can accommodate a variety of chemical inhibitors."

Myxopyronin and corallopyronin appear to work against a broad range of infectious diseases including TB, according to the researchers. The current treatment for TB, rifamycins, requires six months to two years of therapy, depending on whether the person can tolerate the drugs or whether the strain of TB the person has is resistant to antibiotics.

The researchers said that antibiotics targeting this RNA polymerase hinge cut treatment time down to as little as two weeks.

More information

The American Lung Association has more about tuberculosis.

Posted: October 2008


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