Abramov Vyacheslav M, Kosarev Igor V, Machulin Andrey V, Priputnevich Tatiana V, Chikileva Irina O, Deryusheva Evgenia I, Abashina Tatiana N, Donetskova Almira D, Panin Alexander N, Melnikov Vyacheslav G, Suzina Nataliya E, Nikonov Ilia N, Selina Marina V, Khlebnikov Valentin S, Sakulin Vadim K, Vasilenko Raisa N, Samoilenko Vladimir A, Uversky Vladimir N, Karlyshev Andrey V
Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor), Federal State Budgetary Institution "The Russian State Center for Animal Feed and Drug Standardization and Quality" (FGBU VGNKI), 123022 Moscow, Russia.
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health, 117997 Moscow, Russia.
Antibiotics (Basel). 2022 Oct 19;11(10):1437. doi: 10.3390/antibiotics11101437.
strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. The high-quality genome sequencing of LF3872 was performed, and a gene encoding a unique bacteriocin was discovered. It was established that the bacteriocin produced by LF3872 (BLF3872) belongs to the family of cell-wall-degrading proteins that cause cell lysis. The antibacterial properties of LF3872 were studied using test cultures of antibiotic-resistant Gram-positive and Gram-negative pathogens. Gram-positive pathogens ( strain 8325-4 and strain IIE CI-SA 1246) were highly sensitive to the bacteriolytic action of LF3872. Gram-negative pathogens (, strains, and strains) were more resistant to the bacteriolytic action of LF3872 compared to Gram-positive pathogens. LF3872 is a strong co-aggregator of Gram-negative pathogens. The cell-free culture supernatant of LF3872 (CSLF3872) induced cell damage in the Gram-positive and Gram-negative test cultures and ATP leakage. In the in vitro experiments, it was found that LF3872 and Actigen prebiotic (Alltech Inc., Nicholasville, KY, USA) exhibited synergistic anti-adhesive activity against Gram-negative pathogens. LF3872 has immunoregulatory properties: it inhibited the lipopolysaccharide-induced production of proinflammatory cytokines IL-8, IL-1β, and TNF-α in a monolayer of Caco-2 cells; inhibited the production of IL-12 and stimulated the production of IL-10 in immature human dendritic cells; and stimulated the production of TGF-β, IFN-γ, and IgA in the immunocompetent cells of intestinal Peyer's patches (PPs) in mice. These results indicate the possibility of creating a synbiotic based on LF3872 and a prebiotic derived from cell wall components. Such innovative drugs and biologically active additives are necessary for the implementation of a strategy to reduce the spread of antibiotic-resistant strains of socially significant animal and human infections.
菌株3872（LF3872）最初是从一名健康女性哺乳期的母乳以及一名儿童的母乳喂养过程中分离出来的。对LF3872进行了高质量的基因组测序，并发现了一个编码独特细菌素的基因。已确定LF3872产生的细菌素（BLF3872）属于导致细胞裂解的细胞壁降解蛋白家族。使用耐抗生素革兰氏阳性和革兰氏阴性病原体的测试培养物研究了LF3872的抗菌特性。革兰氏阳性病原体（菌株8325 - 4和菌株IIE CI - SA 1246）对LF3872的溶菌作用高度敏感。与革兰氏阳性病原体相比，革兰氏阴性病原体（菌株、菌株和菌株）对LF3872的溶菌作用更具抗性。LF3872是革兰氏阴性病原体的强力共聚集剂。LF3872的无细胞培养上清液（CSLF3872）在革兰氏阳性和革兰氏阴性测试培养物中诱导细胞损伤和ATP泄漏。在体外实验中，发现LF3872和Actigen益生元（美国肯塔基州尼古拉斯维尔的奥特奇公司）对革兰氏阴性病原体表现出协同抗粘附活性。LF3872具有免疫调节特性：它抑制脂多糖诱导的Caco - 2细胞单层中促炎细胞因子IL - 8、IL - 1β和TNF - α的产生；抑制未成熟人树突状细胞中IL - 12的产生并刺激IL - 10的产生；并刺激小鼠肠道派尔集合淋巴结（PPs）免疫活性细胞中TGF - β、IFN - γ和IgA的产生。这些结果表明基于LF3872和源自细胞壁成分的益生元创建合生元的可能性。这种创新药物和生物活性添加剂对于实施减少具有社会重要性的动物和人类感染的抗生素耐药菌株传播的策略是必要的。
