Re-engineered antibiotic could help fight superbugs

Scientists have developed a promising second-generation antibiotic that has shown effectiveness against common drug-resistant bacterial infections that pose a serious health threat.
Researchers led by St Jude Children's Research Hospital scientists created the antibiotics by changing the chemical structure of an old antibiotic named spectinomycin.
Spectinomycin is a safe, but weak drug first introduced in the 1960s.
Investigators built on research published in the 1980s to create new, more potent versions or analogs of spectinomycin.
The analogs include one named 1950 that proved as effective as the antibiotic ampicillin at protecting mice from an often lethal strain of Streptococcus pneumonia.

The bacterium cause pneumococcal infections, including pneumonia, meningitis, the ear infection otitis media and sepsis in humans.

In the laboratory, the spectinomycin analogs blocked the growth of strains of the pneumococcal bacteria resistant to commonly used antibiotics.
The second-generation spectinomycins demonstrated increased antibacterial activity against Haemophilus influenza and Moraxella catarrhalis, which are additional common causes of respiratory infection.
The spectinomycin analogs were also more effective against bacteria responsible for most cases of Legionnaires' disease and the sexually transmitted diseases gonorrhea and chlamydia.
"The growing problem of drug-resistant bacteria has created an urgent need for new antibiotics that use novel mechanisms to treat adults and children worldwide," said corresponding author Richard Lee, a member of the St Jude Department of Chemical Biology and Therapeutics.

Researchers used a structure-based design to map and re-engineer how spectinomycin binds to the ribosomes of clinically important bacteria with a focus on generating compounds that work on a broader spectrum of disease-causing bacteria.
"The re-engineered spectinomycin has a new hook it uses to enter a broad range of bacteria, bind to the ribosome and block protein synthesis," Lee added.
The findings appear in the journal Science Translational Medicine.