Bacitracin is a polypeptide antibiotic produced by organisms of the licheniformis group of Bacillus subtilis var Tracy[1]. Bacitracin inhibits cell wall biosynthesis and permeability through binding to the undecaprenyl pyrophosphate[2]. Bacitracin is typically used in the study of antibacterial mechanisms[3][4].
In vitro, treatment of human melanoma MeWo cells with Bacitracin (1mM; 48h) competitively inhibits dipeptidyl peptidase IV (DPP-IV) and aminopeptidase N (APN), reduces cell viability, and induces DNA fragmentation (sub-G₁ peak elevated to 24.3%) and cell apoptosis[5].
In vivo, Bacitracin (0-100mg/kg; i.m.; once daily for 12 days) markedly suppressed tumor growth, increased the percentages of apoptotic cells, decreased microvessel density and increased central necrotic area in MH134 hepatocellular carcinoma xenografts in C3H mice[6]. Bacitracin (20mg per mouse; p.o.; once daily for 7 days) lowers serum FITC-dextran levels, upregulates ileal ZO-1, JAM-A, occludin and colonic ZO-1, claudin-3, and claudin-4 mRNA expression, and reduces intestinal permeability in C57BL/10 mice[7].
References:
[1] Piepenbreier H, Sim A, Kobras CM, et al. From Modules to Networks: a Systems-Level Analysis of the Bacitracin Stress Response in Bacillus subtilis. mSystems. 2020;5(1):e00687-19.
[2] Economou NJ, Cocklin S, Loll PJ. High-resolution crystal structure reveals molecular details of target recognition by bacitracin. Proc Natl Acad Sci U S A. 2013;110(35):14207-14212.
[3] Buijs NP, Vlaming HC, Kotsogianni I, et al. A classic antibiotic reimagined: Rationally designed bacitracin variants exhibit potent activity against vancomycin-resistant pathogens. Proc Natl Acad Sci U S A. 2024;121(29):e2315310121.
[4] Si W, Wang L, Usongo V, Zhao X. Colistin Induces S. aureus Susceptibility to Bacitracin. Front Microbiol. 2018;9:2805.
[5] Méndez LR, Arrebola Y, Valdés-Tresanco ME, et al. Bestatin and bacitracin inhibit porcine kidney cortex dipeptidyl peptidase IV activity and reduce human melanoma MeWo cell viability. Int J Biol Macromol. 2020;164:2944-2952.
[6] Yu SJ, Yoon JH, Yang JI, et al. Enhancement of hexokinase II inhibitor-induced apoptosis in hepatocellular carcinoma cells via augmenting ER stress and anti-angiogenesis by protein disulfide isomerase inhibition. J Bioenerg Biomembr. 2012;44(1):101-115.
[7] Nevado R, Forcén R, Layunta E, Murillo MD, Grasa L. Neomycin and bacitracin reduce the intestinal permeability in mice and increase the expression of some tight-junction proteins. Rev Esp Enferm Dig. 2015;107(11):672-676.
Bacitracin是由地衣芽孢杆菌Bacillus subtilis var Tracy产生的一种多肽类抗生素[1]。Bacitracin通过与十一异戊烯焦磷酸结合，抑制细胞壁的生物合成与通透性[2]。Bacitracin通常用于抗菌机制的研究[3][4]。
体外实验中，Bacitracin（1mM；48h）可竞争性抑制人黑色素瘤MeWo细胞中的二肽基肽酶IV（DPP-IV）及氨肽酶N（APN），降低细胞活力，诱导DNA碎片化（sub-G₁峰升高至24.3%），并触发细胞凋亡[5]。
体内实验中，Bacitracin（0–100mg/kg；肌肉注射；每日一次，连续12天）显著抑制C3H小鼠MH134肝癌异种移植瘤的生长，提高凋亡细胞比例，降低微血管密度，并扩大肿瘤中心坏死区域[6]。此外，Bacitracin（每只小鼠20mg；灌胃；每日一次，连续7天）可降低C57BL/10小鼠血清FITC-dextran水平，上调回肠ZO-1、JAM-A、occludin及结肠ZO-1、claudin-3和claudin-4的mRNA表达，并减少肠道通透性[7]。