New antibiotic in development

A new drug designed to treat tuberculosis could be the basis for a class of broad-spectrum drugs that act against various bacteria. Interestingly the drug may be capable of evading resistance.

The drug is called SQ109 and it attacks the tuberculosis bacterium. Scientist are looking to see how the drug can be modified to target other pathogens from yeast to malaria. By targeting multiple pathways, the scientists are of the opinion that this reduces the probability of pathogens becoming resistant.

Humans face the very real risk of a future without antibiotics. The implications of this are that life expectancy could fall due to people dying from diseases that are readily treatable today. Over the past year, various reports have been issued which highlight the problem of antibiotic resistant bacteria and the risks to human health.

Different research groups are examining new candidate antibiotics or different ways to get around the phenomenon of resistance. The team behind SQ109 think that the solution is multi-target drugs. Resistance in many cases arises because there's a specific mutation in the target protein so the drug will no longer bind. From this premise, one possible route to attacking the drug resistance problem is to devise drugs that have more than one target in the bacterial cell to attack.

SQ109 appears to block other proteins involved in critical functions in bacteria, fungi and parasites. The drug inhibits two enzymes that make the molecule menaquinone (Vitamin K2), which is involved in generating the microbial cell's energy. SQ109 also has a third action, called uncoupling, which makes the cell membrane permeable. This transforms the microbial cell membrane from a wall to a screen door. Importantly, it seems to have no affect in humans. These three mechanisms constitute the 'multi-targets'.

SQ109 is made by Sequella Inc., a pharmaceutical company. The researchers are working with international collaborators to apply SQ109 analogs against other infectious diseases.

The researchers are based at University of Illinois at Urbana-Champaign. The findings have been reported to the Journal of Medicinal Chemistry, in a paper titled ". Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases".

Posted by Tim Sandle