化膿性鏈球菌是一種具完全溶血性的革蘭氏陽性球菌。在臨床上此菌所引起的疾病，從輕微的咽喉炎、化膿性皰疹，到壞死性肌膜炎、鏈球菌毒性休克症候群等。自從1980年後，在世界各地由A型鏈球菌所引起嚴重的侵入性疾病可說是時有所聞，而引起這些嚴重侵入性疾病的A型鏈球菌在許多國家已有相關報導是由特定的emm基因型和PFGE型態所致，此外，A型鏈球菌紅黴素之抗藥性在世界各國有愈來愈嚴重之趨勢。本論文收集成大附設醫院1990至2002年389株A型鏈球菌，利用emm typing、PFGE染色體基因型，抗紅黴素基因及臨床疾病作整理分析，此外，也針對此菌之熱源性外毒素B與莢膜之表現量探討其與疾病嚴重度之相關性。結果發現在381株中對紅黴素具抗藥性菌株共有187株（49.1%），其中58株（31%）屬cMLS抗藥表現型，127株（67.9%）屬M抗藥表現型及2株屬iMLS抗藥表現型。在這些菌株中emm基因型以emm1、emm4、emm13及emm25為多數，分別佔256株（66.8%）、55株（14.4%）、11株（2.9%）及19株（5.0%）；脈衝式電泳染色體圖譜以J、F、B及A型為主，分別為58 （15%）、40（10.4%）、36（9.3%）及28（7.3%）。其中emm1與emm4在侵入與非侵入性疾病中常被發現。此外，針對1993至2002年所收集之77株猩紅熱菌株，有56株（72.7%）對紅黴素具抗藥性菌株， PFGE A、D、G及J型佔多數分別為7.8、16.9、10.3及32.5%，而emm基因型以emm1及emm4為主，分別為56株（72.7%）及20株（26%）。在1993年到1995之間emm1型成為最主要的emm基因型別（90%），且可能為當時爆發猩紅熱之流行菌株。研究莢膜及熱源性外毒素B與疾病之關係顯示在389株中有25株並不具有水解蛋白能力，但仍能造成嚴重性疾病；而玻尿酸含量低的A型鏈球菌，在疾病上亦可引起嚴重性疾病。綜合以上結果，本研究除了建立A型鏈球菌emm分型及PFGE染色體分型外，同時也提供南台灣A型鏈球菌之流行病學分析以做為公共衛生防疫之參考。此外，我們也發現有少數A型鏈球菌熱源性外毒素B的存在與否和玻尿酸含量之高低並不影響A型鏈球菌造成疾病之能力，推測在這些菌株中造成宿主疾病的嚴重度，可能仍有其他未知之毒力因子存在。

Streptococcus pyogenes is the causative agent of a wide spectrum of disease, ranging from streptococcal pharyngitis and impetigo to life-threatening necrotizing fasciitis and streptococcal toxin-shock syndrome. The resurgence of invasive infections caused by group A streptococcus (GAS) has been noted worldwide since the mid-1980s. Erythromycin-resistant GAS has increased in many countries in the last decade and specific emm types and particular clones have been indicated in several severe diseases. The aims of this project were to analyze the genetic relatedness of 389 clinical isolates of GAS collected from National Cheng-Kung University Hospital during 1990 to 2002. The emm typing, macrolide-resistant genes, pulsed-field gel electrophoresis (PFGE) typing, and clinical manifestations were used to analyze in these strains. In addition, the amounts of hyaluronic acid and streptococcal pyogenic exotoxin B (SPE B) were measured and their correlations with the disease severity were examined.
Among 381 GAS isolates, there were 187 (49.1%) erythromycin- resistant strains in 58 (31%) strains were cMLS phenotype, 127 (67.9%) were M phenotype and 2 strains were iMLS phenotype. emm1, emm4, emm13 and emm25 were most common, harbored by 256 (66.8%), 55 (14.4%), 11 (2.9%) and 19 (5%) isolates, respectively. PFGE pattern J, F, B and A were most common, harbored by 58 (15%), 40 (10.4%), 36 (9.3%) and 28 (7.3%) isolates, respectively.
Among 389 GAS isolates, seventy-seven GAS isolates associated with scarlet fever epidemics occurring between 1993 and 2002 in southern Taiwan were also investigated. Among them, 56 strains (72.7%) were erythromycin-resistant. PFGE pattern A, D, G, and J were most common, harbored by 7.8, 16.9, 10.3 and 32.5%, respectively. emm1 and emm4 also were most common, harbored by 56 (72.7%) and 20 (26%) isolates, respectively. Among them, an emm1 clone was responsible for the epidemics between 1993 and 1995.
The role of hyaluronic acid and SPE B (protease activity) was also investigated. Among 389 strains, 25 strains did not show any protease activity by the skim milk plate analysis and Azocasein assay, whereas 48％ of these strains were isolated from invasive diseases. In addition, the low amount of hyaluronic acid was also detected in the strains isolated from severe disease.
Based on the above data, we are not only establish the emm typing and PFGE typing of GAS in our laboratory, but also report the molecular epidemiology of GAS in southern Taiwan which will be valuable information for public health. In addition, low amount of hyaluronic acid or non-protease activity were detected in several strains of GAS isolated from invasive diseases. This suggests that there are novel virulence factor(s) other than hyaluronic acid or protease activity contributing to the pathogenicithy of GAS in human beings.

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