基于芯片的豬鏈球菌比較基因組學(xué)研究
發(fā)布時間：2018-10-17 08:51
【摘要】：豬鏈球菌是重要的人獸共患致病菌,可感染豬和人引起豬鏈球菌病并導(dǎo)致腦膜炎、敗血癥等嚴(yán)重臨床表現(xiàn)。不同來源的豬鏈球菌致病力有明顯差異,一些菌株具有更強(qiáng)的毒力。根據(jù)豬鏈球菌相關(guān)毒力相關(guān)因子的有無,豬鏈球菌病的流行病學(xué),以及動物實(shí)驗(yàn)研究,致病性豬鏈球菌可分為中等致病株,高致病株,流行株。并且,通常認(rèn)為能夠引起人豬鏈球菌病散發(fā)和暴發(fā)流行的菌株具有高致病性。豬鏈球菌的多位點(diǎn)序列分型(MLST)方案可將豬鏈球菌至少分為181個序列型(ST),其中ST1序列群菌株的致病力明顯強(qiáng)于其它ST型別,屬高致病群。ST1克隆群中的ST7序列型菌株在1998年和2005年曾分別在中國的江蘇省,四川省引起豬鏈球菌病暴發(fā)流行。然而,到目前為止,豬鏈球菌的致病機(jī)制及導(dǎo)致其致病力差異的遺傳學(xué)基礎(chǔ)尚不明確。木研究中,以ST1序列型菌株GZl的基因組序列為參考,我們使用NimbleGen公司的高密度原位合成基因組掃描芯片對31株(包括23個血清型,25個ST型)豬鏈球菌進(jìn)行了比較基因組分析,并采用一個新的算法檢測了菌株間基因組內(nèi)容的差異。每個試驗(yàn)菌株相對GZ1缺失的基因數(shù)49至225不等；共632個基因至少在一個實(shí)驗(yàn)菌株中缺失,共1346個基因存在于所有試驗(yàn)菌株中,組成了豬鏈球菌的核心基因組(core genome),占GZ1基因組的68%。多數(shù)非核心基因呈簇狀分布,其中在兩株以上實(shí)驗(yàn)菌株中發(fā)生缺失的共有62個基因簇,定義為變異區(qū)(regions of difference,RDs);26個RD具有基因組島(Genomic islands,GIs)的特征。聚類和統(tǒng)計分析確認(rèn)8個RD與高致病性顯著相關(guān)。其中3個RD編碼已知的豬鏈球菌毒力相關(guān)因子,包括細(xì)胞外因子(EF),莢膜多糖(CPS)和SrtF菌毛�；谠囼�(yàn)菌株多位點(diǎn)序列分型(MLST)數(shù)據(jù)的群體遺傳學(xué)分析,31個試驗(yàn)菌株分為5個亞群(subpopulation/group);比較62個RD在各亞群的分布特點(diǎn),顯示RD片段在亞群進(jìn)化過程中的演化過程。本研究從基因組學(xué)角度闡明了豬鏈球菌種群的多態(tài)性,發(fā)現(xiàn)了新的高致病相關(guān)基因和基因組島。這些發(fā)現(xiàn)為進(jìn)一步揭示豬鏈球菌的致病機(jī)制,深入認(rèn)識其毒力進(jìn)化過程提供了重要線索。
[Abstract]:Streptococcus suis is an important zoonotic pathogen which can infect pigs and humans and lead to severe clinical manifestations such as meningitis and septicemia. The pathogenicity of Streptococcus suis from different sources was significantly different, and some strains had stronger virulence. According to the factors related to the virulence of Streptococcus suis, the epidemiology of Streptococcus suis and the animal experiment, the pathogenic Streptococcus suis can be divided into moderate pathogenic strain, high pathogenic strain and epidemic strain. Moreover, strains that can cause sporadic and outbreak of human streptococcus suis are thought to be highly pathogenic. Streptococcus suis can be divided into at least 181 (ST), by multi-locus sequence typing (MLST). The virulence of ST1 sequence group strains is obviously stronger than that of other ST types. In 1998 and 2005, ST7 sequenced strains of ST1 clones caused outbreaks of Streptococcus suis in Jiangsu Province and Sichuan Province, respectively. However, the pathogenetic mechanism of Streptococcus suis and the genetic basis for its pathogenicity are unclear. Based on the genomic sequence of ST1 sequence strain GZl, 31 strains of Streptococcus suis (including 23 serotypes and 25 ST types) were analyzed by NimbleGen high-density in situ synthetic genomic scanning microarray. A new algorithm was used to detect the difference of genome content among strains. A total of 632 genes were deleted in at least one strain, and a total of 1346 genes were found in all the tested strains. The core genome (core genome), of Streptococcus suis was 68% of the GZ1 genome. Most of the non-core genes were clustered, of which 62 were found missing in more than two experimental strains, defined as (regions of difference,RDs), and 26 RD were characterized as genomic islands (Genomic islands,GIs). Cluster and statistical analysis confirmed that 8 RD were significantly associated with high pathogenicity. Three known virulence related factors of Streptococcus suis were encoded by RD, including extracellular factor (EF), capsule polysaccharide (CPS) and SrtF pili. Based on the (MLST) data of multilocus sequence typing, 31 strains were divided into 5 subpopulations (subpopulation/group), and the distribution characteristics of 62 RD in each subgroup were compared to show the evolution process of RD fragment in the evolution of subgroup. In this study, the polymorphisms of Streptococcus suis population were elucidated from the perspective of genomics, and a novel highly pathogenic gene and genomic island were found. These findings provide important clues for further understanding the pathogenic mechanism of Streptococcus suis and its virulence evolution.
【學(xué)位授予單位】：中國疾病預(yù)防控制中心
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R378
[Abstract]:Streptococcus suis is an important zoonotic pathogen which can infect pigs and humans and lead to severe clinical manifestations such as meningitis and septicemia. The pathogenicity of Streptococcus suis from different sources was significantly different, and some strains had stronger virulence. According to the factors related to the virulence of Streptococcus suis, the epidemiology of Streptococcus suis and the animal experiment, the pathogenic Streptococcus suis can be divided into moderate pathogenic strain, high pathogenic strain and epidemic strain. Moreover, strains that can cause sporadic and outbreak of human streptococcus suis are thought to be highly pathogenic. Streptococcus suis can be divided into at least 181 (ST), by multi-locus sequence typing (MLST). The virulence of ST1 sequence group strains is obviously stronger than that of other ST types. In 1998 and 2005, ST7 sequenced strains of ST1 clones caused outbreaks of Streptococcus suis in Jiangsu Province and Sichuan Province, respectively. However, the pathogenetic mechanism of Streptococcus suis and the genetic basis for its pathogenicity are unclear. Based on the genomic sequence of ST1 sequence strain GZl, 31 strains of Streptococcus suis (including 23 serotypes and 25 ST types) were analyzed by NimbleGen high-density in situ synthetic genomic scanning microarray. A new algorithm was used to detect the difference of genome content among strains. A total of 632 genes were deleted in at least one strain, and a total of 1346 genes were found in all the tested strains. The core genome (core genome), of Streptococcus suis was 68% of the GZ1 genome. Most of the non-core genes were clustered, of which 62 were found missing in more than two experimental strains, defined as (regions of difference,RDs), and 26 RD were characterized as genomic islands (Genomic islands,GIs). Cluster and statistical analysis confirmed that 8 RD were significantly associated with high pathogenicity. Three known virulence related factors of Streptococcus suis were encoded by RD, including extracellular factor (EF), capsule polysaccharide (CPS) and SrtF pili. Based on the (MLST) data of multilocus sequence typing, 31 strains were divided into 5 subpopulations (subpopulation/group), and the distribution characteristics of 62 RD in each subgroup were compared to show the evolution process of RD fragment in the evolution of subgroup. In this study, the polymorphisms of Streptococcus suis population were elucidated from the perspective of genomics, and a novel highly pathogenic gene and genomic island were found. These findings provide important clues for further understanding the pathogenic mechanism of Streptococcus suis and its virulence evolution.
【學(xué)位授予單位】：中國疾病預(yù)防控制中心
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R378
【參考文獻(xiàn)】
相關(guān)期刊論文 前4條
1 ;Comparative analysis of whole genome structure of Streptococcus suis using whole genome PCR scanning[J];Science in China(Series C:Life Sciences);2008年01期
2 ;Comparative analysis of whole-genome sequences of Streptococcus suis[J];Chinese Science Bulletin;2006年10期
3 沈健,孫建中,尤玉民,朱鳳才,楊華富,胡曉抒,宋亞軍,楊瑞馥;一起人-豬鏈球菌感染性綜合征暴發(fā)的流行病學(xué)調(diào)查[J];中華流行病學(xué)雜志;2001年02期
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