Zosurabalpin is a novel class of tethered macrocyclic peptide antibiotics active against various Acinetobacter baumannii complex (ABC) isolates with the MIC90 values of 0.06-0.5mg/L [1]. Zosurabalpin disrupts the transport of lipopolysaccharide (LPS) by inhibiting the LptB2FGC protein complex, which causes LPS to accumulate to toxic levels inside the cell, ultimately resulting in bacterial death[2]. Zosurabalpin has been widely used to inhibit the proliferation of drug-resistant bacteria in animal models[3].
In vivo, Zosurabalpin treatment via subcutaneous injection at a dose of 60mg/kg every 6 hours for 24 hours significantly reduced bacterial burden and improved survival in a mouse model of A. baumannii-induced pneumonia[4].
References:
[1] Arshad N, Azzam W, Zilberberg M D, et al. Acinetobacter baumannii complex infections: new treatment options in the antibiotic pipeline[J]. Microorganisms, 2025, 13(2): 356.
[2] Wang W J, Dong X M, Li G B. Macrocyclic peptides: up-and-coming weapons to combat antimicrobial resistance[J]. Signal Transduction and Targeted Therapy, 2024, 9(1): 81.
[3] Que W, Deng Z, Gao J. Clinical crusade: zosurabalpin's charge against antibiotic resistance[J]. Trends in Molecular Medicine, 2024, 30(5): 420-422.
[4] Zampaloni C, Mattei P, Bleicher K, et al. A novel antibiotic class targeting the lipopolysaccharide transporter[J]. Nature, 2024, 625(7995): 566-571.