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Kill the germs, spare the ears

4th March 2013


The world needs new antibiotics to overcome the ever
increasing resistance of disease-causing bacteria – but it doesn’t need the
side effect that comes with some of the most powerful ones now available:
hearing loss. Today, researchers report they have developed a new approach
to designing antibiotics that kill even “superbugs” but spare the delicate
sensory cells of the inner ear.

Surprisingly, they have found that apramycin, an antibiotic already used in
veterinary medicine, fits this bill -- setting the stage for testing in
humans.

In a paper published online in the Proceedings of the National Academy of
Sciences, a team from Switzerland, England and the University of Michigan
show apramycin’s high efficacy against bacteria, and low potential for
causing hearing loss, through a broad range of tests in animals. That
testing platform is now being used to evaluate other potential antibiotics
that could tackle infections such as multidrug-resistant tuberculosis.

The research aims to overcome a serious limitation of aminoglycoside
antibiotics, a class of drugs which includes the widely used kanamycin,
gentamicin and amikacin.

While great at stopping bacterial infections, these drugs also cause
permanent partial hearing loss in 20 percent of people who take them for a
short course, and up to 100 percent of people who take them over months or
years, for example to treat tuberculosis or lung infections in cystic
fibrosis.

U-M researcher Jochen Schacht, Ph.D., a professor of biological chemistry
and otolaryngology and director of the Kresge Hearing Research Institute at
the U-M Medical School, has spent decades studying why these drugs cause
this “ototoxicity” – a side effect that makes doctors hesitant to prescribe
them. Hearing damage has also caused patients to discontinue treatment
before their antibiotic prescription is over, potentially allowing
drug-resistant strains of bacteria to flourish.

Schacht has found that the drugs produce damaging free radicals inside the
hair cells of the inner ear. Hair cells, named for the tiny sound-sensing
hairs on their surface, are the linchpin of hearing – and once destroyed,
cannot be regrown.

In the new paper, Schacht and his research group joined teams led by
University of Zurich microbiologist Erik Böttger, and structural biologist
and Nobel Prize winner Venkatraman Ramakrishnan of England’s Medical
Research Council Laboratory of Molecular Biology, as well as scientists from
ETH Zurich. Each team brought its particular expertise to the issue, and
after four years of work they developed and tested this new approach to
designing antibiotics.




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