A novel broad-spectrum antibiotic targets multiple-drug-resistant bacteria with dual binding targets and no detectable resistance
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- Evaluated articles (Rapid Reviews Infectious Diseases)
Abstract
The rapid emergence of difficult-to-treat multidrug-resistant pathogens, combined with the scarcity of antibiotics possessing novel mechanisms, poses a significant threat to global public health. Here, we integrated the synthetic-bioinformatic natural product approach with peptide optimization to unveil the antibiotic-producing potential of Paenibacillaceae bacteria. Our culture-independent approach led to the discovery of paenimycin, a novel 11-mer depsi -lipopeptide featuring an unprecedented dual-binding mechanism. By sequestering the phosphate and hydroxyl groups of lipid A in Gram-negative bacteria, as well as the phosphate groups of teichoic acids in Gram-positive bacteria, paenimycin exhibited potent and broad-spectrum efficacy against MDR pathogens in vitro and in vivo models. Remarkably, paenimycin demonstrates no detectable resistance, favorable pharmacokinetics and low nephrotoxicity, positioning it as a promising candidate for treating serve and urgent MDR infections.
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César de la Fuente
Review 1: "A Novel Broad-spectrum Antibiotic Targets Multiple-drug-resistant Bacteria with Dual Binding Targets and No Detectable Resistance"
The reviewer suggested further structural and biophysical characterization to address the mechanism of action, as well as longer passaging to closer mimic clinical conditions upon which resistance occurs would strengthen the preprint.
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César de la Fuente
Review of "A Novel Broad-spectrum Antibiotic Targets Multiple-drug-resistant Bacteria with Dual Binding Targets and No Detectable Resistance"
Reviewer(s): C de la Fuente (University of Pennsylvania) | 📘📘📘📘📘
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