New study revisits 80-year-old antibiotic that promises to kill drug-resistant bacteria

A powerful weapon against drug-resistant bacteria

According to the researchers, multi-drug resistance is emerging among all types of pathogens. The gram-negative pathogens are particularly problematic as they are quite common causes of infection, plus they have a double cell membrane in contrast to other types of bacteria. 

This double membrane (especially the outer protective layer) creates a significant permeability barrier, making it hard for drugs or antibiotics to reach their targets and act effectively. This is where streptothricins come into play. These antibiotics are derived from a soil bacteria called Actinomyces and can cross both membranes to bind with their target protein. 

James Kirby, one of the study authors and a professor of pathology at Harvard Medical School, told IE, “The promise of streptothricins is that they target protein synthesis in a completely unique way in contrast to existing FDA-approved antimicrobials. This allows them to avoid commonly circulating resistance mechanisms.” 

He further added, “This natural product has been evolved by soil bacteria in order to gain turf in the soil.  In doing, these bacteria have figured out how to make an antibiotic that is really good at penetrating through the gram-negative permeability barrier.”

During their study, the researchers examined two highly purified molecules; streptothricin-D and streptothricin-F. Both these forms can selectively attack drug-resistant gram-negative bacteria, and the former is even more effective against pathogens than the latter. 

However, the toxicity levels in the D-form were not suitable for human kidneys, and therefore the researchers decided to go ahead with the F-form. Next, they tested streptothricin-F in a mouse that carried infection from a highly drug-resistant pathogen, Klebsiella pneumonia.  

The antibiotic successfully adhered to bacterial ribosomes and attacked the target protein. ”We saw great efficacy at levels that were not toxic.  However, we have no knowledge about safety and efficacy in humans. I view our findings as a starting point for the development of streptothricins with an improved activity that may be appropriate for human therapy,” said Kirby.

Streptothricin-F works well against urgent threats 

This study, for the first time, comprehensively profiles the action of the individual components of streptothricins and reveals a purified and safe form of the natural chemical that could actually work against contemporary multi-drug resistant pathogens. According to researchers, previous studies on streptothricins failed to completely purify the chemical. 

Moreover, streptothricin F is highly effective, even against the most dangerous pathogens. “If you look at the CDC list of concerning multidrug-resistant pathogens, as we show in our manuscript, streptothricins are highly active against at least two of the five classified by the CDC as the most urgent threats,” Kirby told IE.

Hopefully, streptothricin-F will emerge as a powerful solution against a variety of multi-drug-resistant bacteria.

The study was published in the journal PLoS Biology.