Iida-Tanaka K, Tanaka T, Irino S, Nagayama A
J Antimicrob Chemother. 1986 Aug;18(2):239-50. doi: 10.1093/jac/18.2.239.
The effects of sub-minimum inhibitory concentrations (sub-MICs) of monobactams (aztreonam and AMA1080) on the host-parasite relationship were studied in an in vitro system using an established mouse macrophage cell line. The presence of sub-MICs aztreonam or AMA1080 enhanced significantly the macrophage bactericidal activity against Escherichia coli S615, Pseudomonas aeruginosa K1, Klebsiella pneumoniae 12 and Serratia marcescens US5. Even four times the MIC of monobactams had no direct effect on macrophages. A synergistic bactericidal effect against E. coli was also observed with sub-MICs of monobactams and lysozyme or macrophage lysate. Furthermore, E. coli treated with sub-MICs of aztreonam was more sensitive to two bactericidal macrophage products, hydrogen peroxide and superoxide anion. These results suggest that the effects of monobactams are exerted on bacteria and not on macrophages; sub-inhibitory levels of monobactams may alter the bacterial cell rendering it more susceptible to bactericidal substances released by macrophages, thus favouring phagocytosis and killing by macrophages. Electron microscopic observations support these conclusions. This study provides evidence that monobactams at sub-MICs may work in partnership with host defenses against Gram-negative bacterial infections.
在体外系统中，使用已建立的小鼠巨噬细胞系，研究了单环β-内酰胺类抗生素（氨曲南和AMA1080）的亚最小抑菌浓度（亚MICs）对宿主-寄生虫关系的影响。亚MICs氨曲南或AMA1080的存在显著增强了巨噬细胞对大肠杆菌S615、铜绿假单胞菌K1、肺炎克雷伯菌12和粘质沙雷氏菌US5的杀菌活性。即使单环β-内酰胺类抗生素的MIC的四倍对巨噬细胞也没有直接影响。单环β-内酰胺类抗生素的亚MICs与溶菌酶或巨噬细胞裂解物对大肠杆菌也观察到协同杀菌作用。此外，用亚MICs氨曲南处理的大肠杆菌对两种杀菌性巨噬细胞产物过氧化氢和超氧阴离子更敏感。这些结果表明，单环β-内酰胺类抗生素的作用是作用于细菌而非巨噬细胞；单环β-内酰胺类抗生素的亚抑制水平可能会改变细菌细胞，使其更容易受到巨噬细胞释放的杀菌物质的影响，从而有利于巨噬细胞的吞噬和杀伤作用。电子显微镜观察支持这些结论。本研究提供了证据表明亚MICs的单环β-内酰胺类抗生素可能与宿主防御革兰氏阴性菌感染协同发挥作用。
