By tweaking the antibiotic spectinomycin, researchers have successfully boosted its effectiveness against six drug-resistant bacteria that cause common respiratory and sexually transmitted diseases (STDs). The antibiotic spectinomycin was originally developed to treat gonorrhoea.
The tweaked drug, tested in vivo and on mice, produced excellent results. Once clinical testing is completed, the repurposed antibiotic can prove to be a boon to public health. The results are published today (May 21) in the journal Science Translational Medicine .
In its old form, the antibiotic is very safe for use but it lacks the necessary antibacterial activity against many bacterial pathogens. As a result, in the U.S., spectinomycin has not been used to treat gonorrhoea since 2005.
While more and more pathogens are showing greater resistance against drugs, the pipelines for new drugs are far from keeping up with them. Repurposing old drugs against these pathogens is therefore very encouraging.
The lead author David F. Bruhn from the St. Jude’s Children’s Research Hospital, Tennessee and others modelled the spectinomycin’s binding site in the bacterial ribosome and later tweaked the drug’s structure so 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.
These were found to be effective against common respiratory tract pathogens — Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila , and Moraxella catarrhalis — as well as the sexually transmitted bacteria — Neisseria gonorrhoeae and Chlamydia trachomatis .
The work “moved the antibacterial activity of the series into a therapeutic range for these agents while also improving pharmacokinetic properties,” they write.
The repurposed antibiotic proved more effective as a result of greater accumulation of the active compound within the bacteria. This was achieved by successfully blocking the efflux pump that removes the active compound from a cell.
In addition to better activity, the repurposed antibiotic had increased chemical stability and pharmacokinetics and had increased half-life. As a request, a lower dose of the tweaked antibiotic was found to be effective in clearing gonorrhoea.
In the case of S. pneumoniae , a predominant cause of childhood upper respiratory tract infection, the tweaked antibiotic proved to be highly efficacious and capable of clearing the pathogens even when lower doses were used.