Genetically modified Streptococcus mutans for the prevention of dental caries
Genetically modified Streptococcus mutans for the prevention of dental caries
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DOI：
10.1023/a:1020695902160
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发表时间：
2002-08-01
影响因子：
2.6
通讯作者：
Hillman, JD
中科院分区：
文献类型：
--
作者：
Hillman, JD
生活在同一生态系统中的不同种类的细菌之间有许多积极和消极的相互作用的例子。这一观察结果为一种称为替代疗法的预防微生物疾病的新方法提供了基础。在这种方法中，一种无害的效应菌株被永久植入宿主的微生物群中。一旦建立，效应菌株的存在可以防止特定病原体的定植或生长。在龋齿的病例中，替代疗法涉及到一种名为BCS3-L1的效应菌株的构建，该菌株来源于一种临床变形链球菌分离物。利用重组DNA技术将BCS3-L1中编码乳酸脱氢酶的基因删除，使其完全缺乏乳酸生成能力。这种效应菌株也被设计成能产生大量的一种叫做诱变素1140的新型肽抗生素，这使它比大多数其他的诱变链球菌菌株具有很强的选择优势。在实验室和啮齿类动物模型研究中，发现BCS3-L1具有遗传稳定性，并且在长期定植过程中不会产生明显的有害副作用。BCS3-L1在无牙生物大鼠中的致龋性明显低于野生型变形链球菌，并且它对传统Sprague-Dawley大鼠本土菌群的致龋性完全没有贡献。而且，其强大的定殖特性表明，将BCS3-L1效应菌株单次应用于人类受试者，就会导致其永久植入，并随着时间的推移被本地致病的变形链球菌菌株取代。因此，预防龋齿的BCS3-L1替代疗法是生物膜工程的一个例子，它为传统预防策略提供了一种高效、经济有效的增强潜力。希望替代疗法预防龋齿的最终成功将刺激这种方法在预防其他细菌性疾病中的应用。
There are many examples of positive and negative interactions between different species of bacteria inhabiting the same ecosystem. This observation provides the basis for a novel approach to preventing microbial diseases called replacement therapy. In this approach, a harmless effector strain is permanently implanted in the host's microflora. Once established, the presence of the effector strain prevents the colonization or outgrowth of a particular pathogen. In the case of dental caries, replacement therapy has involved construction of an effector strain called BCS3-L1, which was derived from a clinical Streptococcus mutans isolate. Recombinant DNA technology was used to delete the gene encoding lactate dehydrogenase in BCS3-L1 making it entirely deficient in lactic acid production. This effector strain was also designed to produce elevated amounts of a novel peptide antibiotic called mutacin 1140 that gives it a strong selective advantage over most other strains of S. mutans. In laboratory and rodent model studies, BCS3-L1 was found to be genetically stable and to produce no apparent deleterious side effects during prolonged colonization. BCS3-L1 was significantly less cariogenic than wild-type S. mutans in gnotobiotic rats, and it did not contribute at all to the cariogenic potential of the indigenous flora of conventional Sprague-Dawley rats. And, its strong colonization properties indicated that a single application of the BCS3-L1 effector strain to human subjects should result in its permanent implantation and displacement over time of indigenous, disease-causing S. mutans strains. Thus, BCS3-L1 replacement therapy for the prevention of dental caries is an example of biofilm engineering that offers the potential for a highly efficient, cost effective augmentation of conventional prevention strategies. It is hoped that the eventual success of replacement therapy for the prevention of dental caries will stimulate the use of this approach in the prevention of other bacterial diseases.