Department of Microbiology, Guiyang Medical College, Guiyang, 550004, China.
J Mater Sci Mater Med. 2012 Jul;23(7):1723-8. doi: 10.1007/s10856-012-4645-z. Epub 2012 Apr 21.
Mammalian β-defensins are small cationic peptides of approximately 2-6 kDa that have been implicated in mediating innate immune defenses against microbial infection. This present study investigated the activity of mouse β-defensin 3 (MBD3) against bacterial and yeast drug-resistant strains in vitro, and whether this molecule acts in synergy with antibiotics. Minimum inhibitory concentrations (MICs) and minimum bactericidal/fungicidal concentrations (MBC/MFC) of recombinant MBD3 (rMBD3) were determined by microdilution assays against different strains of Staphylococcus aureus and Candida albicans. rMBD3 inhibited the growth of S. aureus (MIC, 25 μg/ml) and C. albicans (MIC, 25 μg/ml), and showed fungicidal activity against this yeast (MFC, 100 μg/ml). The influences of rMBD3 on S. aureus and C. albicans cells were examined using electron microscopy. Cells treated with rMBD3 showed morphological and structural changes, including delamination and perforation of the peripheral cell walls, porosity, and inanition of the cytoplasmic contents. Synergistic activities of rMBD3 with different antibiotics were assessed using checkerboard tests. Interestingly, the anti-methicillin-resistant S. aureus activity of rMBD3 in combination with ampicillin was synergistic; however, this was not the case against S. aureus (ATCC 25923). Combinations of rMBD3 with itraconazole, amphotericin or 5-fluorocytosine were synergistic against the two tested C. albicans strains. These results support the interest devoted to defensins as a novel class of antimicrobial agents, and highlight their abilities to potentiate the activities of conventional antibiotics.
哺乳动物 β-防御素是一种约 2-6 kDa 的阳离子小肽，被认为在介导针对微生物感染的先天免疫防御中发挥作用。本研究调查了鼠 β-防御素 3（MBD3）对体外细菌和酵母耐药株的活性，以及该分子是否与抗生素协同作用。通过微量稀释法测定了重组 MBD3（rMBD3）对不同金黄色葡萄球菌和白色念珠菌菌株的最小抑菌浓度（MIC）和最小杀菌/抑菌浓度（MBC/MFC）。rMBD3 抑制了金黄色葡萄球菌（MIC，25 μg/ml）和白色念珠菌（MIC，25 μg/ml）的生长，并对该酵母具有杀菌活性（MFC，100 μg/ml）。使用电子显微镜检查 rMBD3 对金黄色葡萄球菌和白色念珠菌细胞的影响。用 rMBD3 处理的细胞表现出形态和结构变化，包括外周细胞壁的分层和穿孔、多孔性和细胞质内容物的枯竭。使用棋盘试验评估 rMBD3 与不同抗生素的协同作用。有趣的是，rMBD3 与氨苄西林联合使用对耐甲氧西林金黄色葡萄球菌的活性具有协同作用；然而，对金黄色葡萄球菌（ATCC 25923）则不然。rMBD3 与伊曲康唑、两性霉素或 5-氟胞嘧啶联合使用对两种测试的白色念珠菌菌株具有协同作用。这些结果支持将防御素作为一类新型抗菌剂的关注，并强调了它们增强常规抗生素活性的能力。
