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Want to combat antimicrobial resistance: New class of antibiotics may help

New York – A research, published in the journal Nature, has discovered a new class of compounds that combine direct antibiotic killing of pan drug-resistant bacterial pathogens with a simultaneous rapid immune response for combating antimicrobial resistance.
It has come to fore when the list of bacteria that are becoming resistant to treatment with all available antibiotic options is growing and few new drugs are in the pipeline, creating a pressing need for new classes of antibiotics to prevent public health crises.
Farokh Dotiwala, Assistant Professor in the Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, US, said: “We took a creative, double-pronged strategy to develop new molecules that can kill difficult-to-treat infections while enhancing the natural host immune response.” Dotiwala, lead author of the effort to identify a new generation of antimicrobials named dual-acting immuno-antibiotics (DAIAs) said existing antibiotics target essential bacterial functions, including nucleic acid and protein synthesis, building of the cell membrane, and metabolic pathways.
He added: “We reasoned that harnessing the immune system to simultaneously attack bacteria on two different fronts makes it hard for them to develop resistance.” The researchers focused on a metabolic pathway called methyl-D-erythritol phosphate (MEP) or non-mevalonate pathway, is responsible for biosynthesis of isoprenoids — molecules required for cell survival in most pathogenic bacteria.
The lab targeted the IspH enzyme, an essential enzyme in isoprenoid biosynthesis, as a way to block this pathway and kill the microbes. Given the broad presence of IspH in the bacterial world, this approach may target a wide range of bacteria. Researchers used computer modeling to screen several million commercially available compounds for their ability to bind with the enzyme, and selected the most potent ones that inhibited IspH function as starting points for drug discovery.

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