Bratt Carol L, Kohlgraf Karl G, Yohnke Katie, Kummet Colleen, Dawson Deborah V, Brogden Kim A
Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
Probiotics Antimicrob Proteins. 2010 Mar 1;2(1):21-5. doi: 10.1007/s12602-009-9028-5.
Antibiotic therapy is often used with mechanical therapy to treat periodontal disease. However, complications associated with antibiotic use can occur. A 'bacteria-specific' targeted approach would eliminate some of these complications and kill specific periodontopathogens without harming the commensal bacteria. One such approach is to couple antimicrobial peptides to a ligand, pheromone, or antibody specific for the periodontopathogen, Porphyromonas gingivalis. To assess the feasibility of this approach, we attached PQGPPQ, a peptide from proline-rich protein 1 to either the N-terminus of SMAP28 (peptide ZS37-37) or the C-terminus of SMAP28 (peptide ZS37-38) to see whether it has potential as a carrier ligand to deliver SMAP28 to the surface of P. gingivalis. For Escherichia coli and Aggregatibacter actinomycetemcomitans, the median minimal inhibitory concentration (MIC) of ZS37-37 was higher than the median of SMAP28 alone, although the median MIC of ZS37-38 was lower than that of SMAP28 alone. For P. gingivalis, there was no difference in the median MIC values. For S. aureus, the median MIC was higher for ZS37-37 and ZS37-38 compared to SMAP28 alone, particularly for ZS37-38. For Fusobacterium nucleatum, the median MIC values were equal for ZS37-37 and ZS37-38 and higher than the median MIC for SMAP28 alone. Attaching PQGPPQ to SMAP28 did not greatly increase the antimicrobial activity of ZS37-37 or ZS37-38 for P. gingivalis nor substantially decrease the antimicrobial activity of ZS37-37 or ZS37-38 for the four other microorganisms tested. This is an initial step to develop a selective antimicrobial agent that has 'targeted' antimicrobial activity without adverse reactions often associated with the use of broad-spectrum antibiotics.
抗生素疗法常与机械疗法联合用于治疗牙周疾病。然而，使用抗生素可能会出现相关并发症。一种“细菌特异性”靶向方法可以消除其中一些并发症，并杀死特定的牙周病原体，同时不伤害共生细菌。一种这样的方法是将抗菌肽与对牙周病原体牙龈卟啉单胞菌具有特异性的配体、信息素或抗体偶联。为了评估这种方法的可行性，我们将富含脯氨酸蛋白1的肽PQGPPQ连接到SMAP28的N端（肽ZS37 - 37）或C端（肽ZS37 - 38），以观察其作为载体配体将SMAP28递送至牙龈卟啉单胞菌表面的潜力。对于大肠杆菌和伴放线聚集杆菌，ZS37 - 37的中位最小抑菌浓度（MIC）高于单独的SMAP28的中位值，尽管ZS37 - 38的中位MIC低于单独的SMAP28。对于牙龈卟啉单胞菌，中位MIC值没有差异。对于金黄色葡萄球菌，与单独的SMAP28相比，ZS37 - 37和ZS37 - 38的中位MIC更高，特别是ZS37 - 38。对于具核梭杆菌，ZS37 - 37和ZS37 - 38的中位MIC值相等且高于单独的SMAP28的中位MIC。将PQGPPQ连接到SMAP28上，对于牙龈卟啉单胞菌，并没有显著增加ZS37 - 37或ZS37 - 38的抗菌活性，对于其他四种测试微生物，也没有显著降低ZS37 - 37或ZS-38的抗菌活性。这是开发一种具有“靶向”抗菌活性且无通常与使用广谱抗生素相关的不良反应的选择性抗菌剂的初步步骤。
