Wistar Institute (Philadelphia) scientists have discovered a new class of compounds that uniquely combine direct antibiotic killing of pan drug-resistant bacterial pathogens with a simultaneous rapid immune response for combatting antimicrobial resistance (AMR). These finding were published online on December 23, 2020 in Nature. The article is titled “IspH inhibitors Kill Gram-Negative Bacteria and Mobilize Immune Clearance.” The World Health Organization (WHO) has declared antimicrobial resistance (AMR) as one of the top 10 global public health threats against humanity. It is estimated that by 2050, antibiotic-resistant infections could claim 10 million lives each year and impose a cumulative $100 trillion burden on the global economy. 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. “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,” said Farokh Dotiwala, M.B.B.S., Ph.D., Farokh Dotiwala (https://wistar.org/our-scientists/farokh-dotiwala), MBBS, PhD, Assistant Professor in the Vaccine & Immunotherapy Center and lead author of the effort to identify a new generation of antimicrobials named dual-acting immuno-antibiotics (DAIAs). Existing antibiotics target essential bacterial functions, including nucleic acid and protein synthesis, building of the cell membrane, and metabolic pathways. However, bacteria can acquire drug resistance by mutating the bacterial target the antibiotic is directed against, inactivating the drugs, or pumping them out.
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