Researchers have tweaked an old antibiotic and boosted its effectiveness against six different drug-resistant bacteria that cause common respiratory and sexually transmitted diseases. With further clinical testing, the drug could offer a new treatment option for resistant bacterial infections, which have emerged as a major public health threat worldwide.
The antibiotic spectinomycin was originally developed to treat gonorrhoea. It blocks bacterial growth by disrupting protein synthesis in the ribosome. Though safe, spectinomycin has only weak antibacterial activity and was eventually removed from the market.
David Bruhn, health outcomes liaison at GlaxoSmithKline and colleagues revisited the drug, seeking to enhance its potency. Using computational modelling of spectinomycin's binding site in the bacterial ribosome, the researchers tweaked the drug's structure so that it could bind to the ribosomes of a variety of bacteria. By substituting a benzyl molecule, they created six compounds that form a new class of antibiotics that they called aminomethyl spectinomycins.
Testing the compounds against a wide range of bacteria in culture, the researchers found that the new antibiotics proved superior to the original spectinomycin. The new compounds were effective against a particularly resistant strain of Streptococcus pneumoniae that resists many existing drugs.
The antibiotics also treated five other bacteria that cause the sexually transmitted diseases gonorrhoea, a multidrug-resistant infection, and chlamydia, as well as respiratory tract infections, including pneumonia and influenza. In mice with lethal infections of a strain of S. pneumonia that causes pneumonia and bloodstream infection, low doses of aminomethyl spectinomycin cleared infection and prolonged survival. Rats treated with the antibiotic showed no serious side effects.
The findings support further development of this new class of antibiotics, which may provide a new way of treating drug-resistant respiratory and sexually transmitted infections.
[link url="http://www.sciencemag.org/"]Science Mag material[/link]
[link url="http://stm.sciencemag.org/content/7/288/288ra75"]Science Translational Medicine abstract[/link]