Polymyxin B nonapeptide

Polymyxin B nonapeptide, as a cationic cyclic peptide derived from polymyxin B, can increase the permeability of the outer membrane (OM) of GNB toward hydrophobic antibiotics probably. Polymyxin B nonapeptide has less toxicity and no bactericidal activity^[1].

In vitro cytotoxicity experiments, Polymyxin B nonapeptide show IC50 with >32 µg/ml in FBS, MDCK, HaCaT and HEK 239 cell lines^[2]. In vitro experiment it shown that at 32 and 16 µg/ml Polymyxin B nonapeptide with > 4 µg/ml azithromycin can kill bacterial. While at 8, 4 and 2 µg/ml Polymyxin B nonapeptide in combination with > 8 µg/ml azithromycin also caused same effect^[1]. In vitro, smooth Salmonella typhimurium had a binding capacity of ca. 6 nmol of Polymyxin B nonapeptide per mg (dry weight) of bacteria, which is equivalent to ca. 1 X 106 to 2 X 106 molecules of Polymyxin B nonapeptide per single cell. The binding was of relatively high affinity with Kd of 1.3 µM. In addition, the isolated outer membrane of S. typhimurium bound ca. 100 nmol of Polymyxin B nonapeptide per mg of outer membrane protein with Kd of 1.1 µM, whereas the cytoplasmic membrane bound 9 to 10 times less^[3]. In vitro, with 4 µg/ml Polymyxin B nonapeptide can increase electrotransformation efficiency of the growth of uropathogenic E. coli^[4].

In vivo experiment it shown that polymyxin B nonapeptide with 1.5 and 3.0 mg/kg did not exhibit the neuromuscular blocking, neurotoxic, or nephrotoxic effects^[5].

References:

[1]Al-Marzooq F, et al. Discerning the role of polymyxin B nonapeptide in restoring the antibacterial activity of azithromycin against antibiotic-resistant Escherichia coli. Front Microbiol. 2022 Sep 21;13:998671.
[2] Khazandi M, et al. In vitro Antimicrobial Activity of Robenidine, Ethylenediaminetetraacetic Acid and Polymyxin B Nonapeptide Against Important Human and Veterinary Pathogens. Front Microbiol. 2019 Apr 25;10:837.
[3] Vaara M, et al. Binding of polymyxin B nonapeptide to gram-negative bacteria. Antimicrob Agents Chemother. 1985 Apr;27(4):548-54.
[4] Qin J, et al. A method for increasing electroporation competence of Gram-negative clinical isolates by polymyxin B nonapeptide. Sci Rep. 2022 Jul 8;12(1):11629.
[5] Danner RL, et al. Purification, toxicity, and antiendotoxin activity of polymyxin B nonapeptide. Antimicrob Agents Chemother. 1989 Sep;33(9):1428-34.