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].

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.

References:

多粘菌素 B 九肽作为衍生自多粘菌素 B 的阳离子环肽,可能会增加 GNB 外膜 (OM) 对疏水性抗生素的通透性。多粘菌素B九肽毒性较小,无杀菌活性^[1]。

在体外细胞毒性实验中,多粘菌素 B 九肽在 FBS、MDCK、HaCaT 和 HEK 239 细胞系^[2] 中的 IC50 为 >32 μg/ml。体外实验表明,在 32 和 16 μg/ml 的多粘菌素 B 九肽中,具有 >； 4 μg/ml 阿奇霉素可杀灭细菌。在 8、4 和 2 μg/ml 多粘菌素 B 九肽与 > 组合时； 8 μg/ml 阿奇霉素也有同样的作用^[1]。在体外,光滑的鼠伤寒沙门氏菌具有约 10 的结合能力。每 mg（干重）细菌含 6 nmol 多粘菌素 B 九肽,相当于 ca。每个单细胞 1 X 106 至 2 X 106 个多粘菌素 B 九肽分子。该结合具有相对较高的亲和力,Kd 为 1.3 μM。此外,鼠伤寒沙门氏菌的分离外膜结合约。每 mg 外膜蛋白加入 100 nmol 多粘菌素 B 九肽,Kd 为 1.1 μM,而胞质膜结合减少 9 至 10 倍^[3]。在体外,4 μg/ml Polymyxin B nonapeptide 可提高尿路致病性大肠杆菌生长的电转化效率^[4]。

体内实验表明,1.5 和 3.0 mg/kg 的多粘菌素 B 九肽没有表现出神经肌肉阻滞、神经毒性或肾毒性作用^[5]。

Al-Marzooq F 等人。辨别多粘菌素 B 九肽在恢复阿奇霉素对抗生素耐药大肠杆菌的抗菌活性中的作用。前微生物。 2022 年 9 月 21 日；13:998671。

^[2] Khazandi M 等人。 Robenidine、乙二胺四乙酸和多粘菌素 B 九肽对重要人类和兽医病原体的体外抗菌活性。前微生物。 2019 年 4 月 25 日；10:837。

^[3] Vaara M 等人。多粘菌素 B 九肽与革兰氏阴性菌的结合。抗菌剂化疗。 1985 年 4 月；27(4):548-54。

^[4] 秦杰等。一种通过多粘菌素 B 九肽提高革兰氏阴性临床分离株电穿孔能力的方法。科学报告 2022 年 7 月 8 日；12(1):11629。

^[5] Danner RL 等人。多粘菌素 B 九肽的纯化、毒性和抗内毒素活性。抗菌剂化疗。 1989 年 9 月；33(9):1428-34。