Designer broad-spectrum polyimidazolium antibiotics
Wenbin Zhong, Zhenyu Shi, Surendra H. Mahadevegowda, Bo Liu, Kaixi Zhang, Chong Hui Koh, Lin Ruan, Yahua Chen, Merve S. Zeden, Carmen J. E. Pee, Kalisvar Marimuthu, Partha Pratim De, Oon Tek Ng, Yabin Zhu, Yonggui Robin, Paula T. Hammond, Liang Yang, Yunn‐Hwen Gan, Kévin Pethe, E. Peter Greenberg, Angelika Gründling, Mary B. Chan‐Park
Abstract
PIM1-resistant mutants did not emerge. Although PIM1 was efficacious as a topical agent, intraperitoneal administration of PIM1 in mice showed some toxicity. We synthesized a PIM1 derivative, PIM1D, which is less hydrophobic than PIM1. PIM1D did not show evidence of toxicity but retained antibacterial activity and showed efficacy in murine sepsis infections. Our evidence indicates the PIMs have potential as candidates for development of new drugs for treatment of pan-resistant bacterial infections.