Franzman Michael R, Burnell Kindra K, Dehkordi-Vakil Farideh H, Guthmiller Janet M, Dawson Deborah V, Brogden Kim A
Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
Int J Antimicrob Agents. 2009 Jan;33(1):14-20. doi: 10.1016/j.ijantimicag.2008.05.021. Epub 2008 Sep 7.
Antimicrobial peptides coupled to a ligand, receptor or antibody for a specific pathogenic bacteria could be used to develop narrow-spectrum pharmaceuticals with 'targeted' antimicrobial activity void of adverse reactions often associated with the use of broad-spectrum antibiotics. To assess the feasibility of this approach, in this study sheep myeloid antimicrobial peptide (SMAP) 28 was linked to affinity- and protein G-purified rabbit immunoglobulin G (IgG) antibodies specific to the outer surface of Porphyromonas gingivalis strain 381. The selective activity of the P. gingivalis IgG-SMAP28 conjugate was then assessed by adding it to an artificially generated microbial community containing P. gingivalis, Aggregatibacter actinomycetemcomitans and Peptostreptococcus micros. The specificity of the P. gingivalis IgG-SMAP28 conjugate in this mixed culture was concentration-dependent. The conjugate at 50 microg protein/mL lacked specificity and killed P. gingivalis, A. actinomycetemcomitans and P. micros. The conjugate at 20 microg protein/mL was more specific and killed P. gingivalis. This is an initial step to develop a selective antimicrobial agent that can eliminate a specific periodontal pathogen, such as P. gingivalis, from patients with periodontal disease without harming the normal commensal flora.
与针对特定病原菌的配体、受体或抗体偶联的抗菌肽，可用于开发具有“靶向”抗菌活性的窄谱药物，这类药物没有使用广谱抗生素时常出现的不良反应。为评估该方法的可行性，在本研究中，将绵羊髓系抗菌肽（SMAP）28与经亲和纯化及蛋白G纯化的、针对牙龈卟啉单胞菌381株外表面的兔免疫球蛋白G（IgG）抗体相连接。然后，通过将牙龈卟啉单胞菌IgG-SMAP28偶联物添加到一个人工构建的包含牙龈卟啉单胞菌、伴放线聚集杆菌和微小消化链球菌的微生物群落中，来评估其选择性活性。在这种混合培养物中，牙龈卟啉单胞菌IgG-SMAP28偶联物的特异性呈浓度依赖性。蛋白质浓度为50微克/毫升的偶联物缺乏特异性，能杀死牙龈卟啉单胞菌、伴放线聚集杆菌和微小消化链球菌。蛋白质浓度为20微克/毫升的偶联物更具特异性，能杀死牙龈卟啉单胞菌。这是开发一种选择性抗菌剂的第一步，该抗菌剂能够在不损害正常共生菌群的情况下，从牙周病患者体内清除特定的牙周病原体，如牙龈卟啉单胞菌。
