Dual-Acting Antibiotics Offer Hope Against Superbugs

Researchers from Wistar Institute have found a new category of compounds that merge the killing of bacterial pathogens that are drug resistant through the use of antibiotics, with a swift immune response used to fight antimicrobial resistance.

Last year, the WHO declared antimicrobial resistance (AMR) as a top public health threat. Estimates show that by the year 2050, infections that are antibiotic resistant could not only thrust upon the world economy a collective burden of $100 trillion but also claim the lives of nearly 10 million people every year. It does not help that the number of bacteria growing treatment resistant with the current antibiotics is increasing, with few new drugs in development. This has created a desperate need for better antibiotics to be developed in a bid to avert public health crisis.

The lead author of the study, who also happens to be an assistant professor in the Vaccine and Immunotherapy Center, Farokh Dotiwala explained that the researchers used a bilateral and creative approach to create novel molecules that may be used to eliminate infections that are challenging to treat while also boosting an individual’s immune response. The main objective of the study was to discover dual-acting immune antibiotics. The study’s findings were reported in the “Nature” journal.

The antibiotics being used at the moment typically target vital bacterial functions such as metabolic pathways, as well as protein and nucleic acid synthesis. However, through bacterial mutations that the antibiotics target, bacteria can gain a resistance to the drugs. This either pumps the drugs out or inactivates them.

Dotiwala stated that the scientists rationalized that using the immune system to target bacteria in different areas at the same time would make it difficult for the bacteria to develop resistance to the antibiotics.

Dotiwala and his colleagues centered their focus on a non-mevalonate pathway that is not present in humans but is vital for a majority of bacteria. This made it the best target for development of antibiotics. The pathway is in charge of the biogenesis of molecules needed in a majority of pathogenic bacteria for cell survival.

Dotiwala then partnered with the other senior author of the study and Wistar’s medicinal chemist Joseph Salvino to discover and synthesize novel molecules of IspH inhibitors that could penetrate the cell walls of the bacteria.

This approach helped the researchers show that the inhibitors triggered stronger bacterial elimination activity in the immune system. The first author of the study, Kumar Singh, explained that activation of the immune system made up another line of defense of the dual-acting immuno-antibiotics strategy.

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