B群鏈球菌常引起新生兒及懷孕婦女的敗血症，近年來的研究也指出此菌造成老年人及免疫不全病人的感染有上升的趨勢。到目前為止，已經發現許多B群鏈球菌的毒力因子，其中表面蛋白質中有一類較特殊的蛋白質，名為Alp family proteins，其基因序列裡有一段相似度相當高的重複性片段。-C蛋白質和Rib蛋白質屬於Alp family proteins的成員之一，研究顯示基因序列裡具有重複性片段的存在，可以幫助病原菌增加抗原變異性，藉此逃脫宿主的攻擊。由於台灣地區對於B群鏈球菌的流病資料相當少，故本論文研究的目的為（1）針對南台灣B群鏈球菌侵襲性臨床菌株，進行莢膜血清型及脈衝式電泳分型之流病調查。（2）探討-c和rib基因中重複性片段數目的多寡。（3）探討在小孩與成人的菌株中基因型和表現型之間的關聯性。（4）探討Rib蛋白質在B群鏈球菌感染中所扮演的角色。本論文所研究的B群鏈球菌來自成大醫院細菌室，自1995-2005年總共58株菌血症的菌株，其中26株的來源為小孩，32株為成人。在58株中，莢膜血清型第III型（46.6%）及第V型（24.1%）最為常見；而脈衝式電泳則發現有10種不同的型別，其中第1型（25.9%）及第10型（17.2%）較為常見。利用聚合酶連鎖反應偵測-c和rib基因重複性片段的數目發現在rib基因有24株表現較多的重複性片段（6-8個重複），而在-c基因則有9株表現較多的重複性片段。rib基因在小孩的菌株比成人的菌株表現較多重複性片段的數目（73.1% VS 15.6%），而在-c基因上並無統計上差異。此外，在小孩的菌株中，其莢膜血清型以第III型（76.9%），脈衝式電泳以第1型（53.8%）為主。為了探討Rib蛋白質在B群鏈球菌感染中所扮演的角色，利用插入法將rib基因進行突變，並以南方墨點法及RT-PCR確認突變株的正確性，此突變株並無影響其下游基因，而野生株與突變株的生長曲線亦無差異。當野生株與突變株和全血及血清共同培養3小時後，突變株抵抗全血清除的能力比野生株少了5倍，但抵抗血清的能力兩者並沒有差異。此外，突變株吸附到人類上皮細胞的能力比野生株少了65%，而侵入細胞的能力並沒有影響。本研究顯示在南台灣B群鏈球菌莢膜血清型第III型、脈衝式電泳第1型及rib基因的多重複性片段與小孩的侵襲性感染有關，而rib基因的表現與細菌的附著及抵抗全血殺菌能力有關。

　Streptococcus agalactiae (group B streptococcus, GBS) is the commonest cause of neonatal and obstetric sepsis. In recent study, GBS becomes an important pathogen in the elderly as well as the immunocompromised host. It has been reported GBS has several virulence factors, such as capsule, surface protein, beta-hemolysin and CAMP factor etc. The Alp family proteins, including C alpha and Rib proteins, are characterized by the extended region composed of long, completely identical repeats. Recent reports suggest that different tandem repeats of C alpha and Rib proteins are associated with antigen variation. Due to lack of GBS epidemiological information in Taiwan, the aims of this study were (i) to determine the capsular serotype and pulsed-field gel electrophoresis (PFGE) pattern in southern Taiwan; (ii) to determine the number of tandem repeats in the α-c and rib genes; (iii) to determine the correlation between genotype and phenotype in infant and adult isolates; (iv) to determine the effect of rib gene on GBS infection. A total of 58 GBS clinical isolates from blood cultures (1995-2005), including 26 from infants and 32 from adults, were collected. Capsule serotypes III (46.6%) and V (24.1%) were most common. Ten different PFGE patterns were found and PFGE types 1 (25.9%) and 10 (17.2%) were most common. The tandem repeats were determined by the PCR analysis. Twenty-four isolates expressed high tandem repeats (6-8 copies) in the rib gene and 9 expressed high tandem repeats in the α-c gene. The high tandem repeats of the rib gene in infant strains (73.1%) were significantly higher than in adult strains (15.6%) but such situation was not found in the α-c gene. The high tandem repeats of rib among infant strains were more associated with capsule type III (76.9%) and PFGE type 1 (53.8%). These data indicate that surface protein Rib could play a role to cause infant severe infection. In order to investigate the effect of rib gene on GBS infection, we constructed a rib isogenic mutant by using integrational mutagenesis to disrupt the rib gene and confirmed by Southern blot and RT-PCR. No polar effect on the downstream gene of rib was detected by using RT-PCR analysis. The growth curves of wild-type strain and rib mutant strain were similar. When incubated with human whole blood or serum, the mutant strain showed five-fold decrease compared to the wild-type strain in whole blood bactericidal assay but little difference in serum bactericidal assay. In addition, the adhesion ability of the mutant to human epithelial cells was about 65% less than that of the wild-type strain, whereas little difference was found in the invasion ability. In summary, we demonstrated that capsule type III, PFGE type 1 and high tandem repeats of rib gene in GBS are associated with infant severe infection in southern Taiwan. The expression of rib gene is important for bacteria adhesion to host cells and anti-whole blood bactericidal activity.

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