Burne R A, Chen Y Y, Wexler D L, Kuramitsu H, Bowen W H
Department of Dental Research, University of Rochester Medical Center, New York 14642, USA.
J Dent Res. 1996 Aug;75(8):1572-7. doi: 10.1177/00220345960750080801.
To define the role of dental plaque fructans and the enzymes involved in their metabolism in the initiation and progression of dental caries, we constructed otherwise-isogenic mutants of Streptococcus mutans defective in the ability to synthesize fructans, to degrade fructans, or to do both. The cariogenic potential of these organisms was evaluated in a specific-pathogen-free rat model in which the feeding patterns of the animals were controlled by means of a König-Hofer programed feeder. Specifically, rats were infected with wild-type S. mutans UA159 or derivatives of this strain which contained an insertionally-inactivated fructanase (fruA) gene, fructosyltransferase (ftf) gene, or which had both genes inactivated. The animals were fed 17 meals per day of Diet 2000 containing 56% sucrose at 70-minute intervals for five weeks, and caries experience was evaluated. Animals infected with S. mutans with a mutated fruA gene only had statistically significant decreases in sulcal caries severity. Such a decrease was not observed in previous studies with ad libitum-fed animals (Wexler et al., 1992). The manifestation of diminished virulence in the programmed feeding model, but not in ad libitum-fed animals, supports the concept that the primary contribution of FruA to virulence is through the utilization of fructans storage polysaccharides. Animals infected with strains carrying the ftf mutation or simultaneous mutations in ftf and fruA did not display decreased virulence, perhaps indicating that sucrose utilization pathways may compete for substrate in vivo, or that accumulation of fructans may affect the ecology or the physicochemical characteristics of dental plaque in such a way as to reduce its cariogenic potential. The results of this study also emphasize that the contribution of a particular virulence determinant to the caries process may be highly dependent on the experimental design, feeding regimen and diet, and the presence or absence of other enzymatic activities.
为了确定牙菌斑果聚糖及其代谢相关酶在龋齿发生和发展中的作用，我们构建了变形链球菌的同基因突变体，这些突变体在合成果聚糖、降解果聚糖或两者兼有的能力方面存在缺陷。在无特定病原体的大鼠模型中评估了这些生物体的致龋潜力，在该模型中，动物的进食模式通过König-Hofer程控喂食器进行控制。具体而言，将大鼠感染野生型变形链球菌UA159或该菌株的衍生物，这些衍生物含有插入失活的果聚糖酶（fruA）基因、果糖基转移酶（ftf）基因，或两个基因均失活。动物每天以70分钟的间隔喂食17餐含56%蔗糖的2000号饮食，持续五周，并评估龋齿情况。仅感染了fruA基因突变的变形链球菌的动物，其沟裂龋严重程度有统计学意义的降低。在先前对自由采食动物的研究中未观察到这种降低（Wexler等人，1992年）。在程控喂食模型中而非自由采食动物中出现的毒力降低现象，支持了FruA对毒力的主要贡献是通过利用果聚糖储存多糖这一概念。感染携带ftf突变或ftf和fruA同时突变菌株的动物未表现出毒力降低，这可能表明蔗糖利用途径在体内可能竞争底物，或者果聚糖的积累可能以降低其致龋潜力的方式影响牙菌斑的生态或物理化学特性。本研究结果还强调，特定毒力决定因素对龋齿过程的贡献可能高度依赖于实验设计、喂食方案和饮食，以及其他酶活性的存在与否。
