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1、Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉细菌学总论第3章细菌遗传与变异 BacterialGeneticsDepartment of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉第一节与细菌遗传相关的物质n细菌染色体n染色体以外的遗传物质u质粒u噬菌体u转座子
2、Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉细菌染色体n细菌染色体chromosomeu一条环状双螺旋DNA长链u按一定构型反复回旋而成的松散网状结构u携带大部分遗传信息，决定细菌基因型u单拷贝，很少有重复序列u连续，无内含子Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical
3、University 张文莉张文莉质粒（plasmid）n概念u染色体以外的遗传物质，存在于细胞质中，具有自主复制的能力，为闭合环状的双链DNA分子，带有遗传信息，控制细菌的某些特定遗传性状Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉质粒(plasmid)n特点u自主复制u不是生长繁殖必需的u编码某些表型u可丢失、转移或消除n分类u接合作用接合性、非接合性u不相容性相容性、不相容性u表型F质粒、R质粒、Vi质粒、C
4、ol质粒Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉噬菌体（bacteriophageorphage）n是侵噬细菌或真菌的病毒，也是赋予宿主菌生物学性状的遗传物质n核酸和蛋白质组成，活菌内寄生，严格宿主特异性n蝌蚪形、球形、杆状Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical
5、 University 张文莉张文莉噬菌体结构n头部核心：DNA或RNA衣壳：蛋白质n尾部蛋白质与吸附宿主有关Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉噬菌体感染细菌的结果n溶菌性周期u毒性噬菌体n溶原性周期u前噬菌体u溶原性细菌u温和噬菌体Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin
6、 Medical University 张文莉张文莉噬菌体的复制Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉溶菌周期n吸附阶段n生物合成阶段n释放阶段Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉prophage:整合在细菌基因组中的噬菌
7、体基因组溶原性细菌前噬菌体温和噬菌体可具有溶原、溶菌两个周期Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉n溶原性细菌u带有前噬菌体基因组的细菌n溶原性转换u有些前噬菌体可使溶原性细菌表型发生改变u无毒的beta-棒状杆菌携带-棒状杆菌噬菌体时成为溶原性细菌，产生白喉毒素致病Department of Microbiology, Harbin Medical UniversityDepartment of Micro
8、biology, Harbin Medical University 张文莉张文莉Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉转座子n转座子transposon,Tnu一类能在细菌的染色体、质
9、粒或噬菌体之间自行移动的遗传物质u功能：插入突变u类型插入序列复合转座子转座酶转座酶ABCDEFGGFEDCBA800-1400bp800-1400bpDepartment of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉第二节细菌的变异现象n形态结构变异：细菌L型、H-O变异n抗原性变异n菌落变异：S-R变异n毒力变异n耐药性变异Department of Microbiology, Harbin Medical UniversityDe
10、partment of Microbiology, Harbin Medical University 张文莉张文莉形态变异3-6%食盐鼠疫杆菌 多形态性(衰残型) 琼脂培基Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉 L型变异-药物、抗体或补体等正常霍乱弧菌霍乱弧菌L型Department of Microbiology, Harbin Medical UniversityDepartment of Microb
11、iology, Harbin Medical University 张文莉张文莉毒力变异Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉卡介苗（BCG）n卡-介（Calmette-Grin）二氏将有毒力的牛型结核分枝杆菌在含胆汁、甘油和马铃薯的培养基上经13年传230代，得到毒力减弱而抗原性稳定的菌株，用于结核病的预防。Department of Microbiology, Harbin Medical Univers
12、ityDepartment of Microbiology, Harbin Medical University 张文莉张文莉第三节 细菌变异机制一、突变n类型u点突变一个碱基对u多点突变两个以上碱基对的变化n回复突变和抑制突变u正向突变u回复突变u抑制突变Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉n突变染色体突变类型染色体突变类型染色体突变类型染色体突变类型A A A AG G G G、X X X X代表不同的
13、代表不同的代表不同的代表不同的DNADNADNADNA片段片段片段片段 野生型野生型倒位倒位重复重复缺失缺失置换置换插入插入Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉二、基因转移和重组n基因转移u供体菌DNA转移给受体菌的过程n基因重组u进入受体菌的外源DNA能够复制，导致其基因型发生改变成为重组体或重组菌n方式u转化、接合、转导、溶原性转换、原生质体融合Department of Microbiology, H
14、arbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉转化概念：受体菌直接摄取供体菌DNA而获得新的遗传性状的过程。Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉转化transformation肺炎链球菌的转化试验肺炎链球菌的转化试验肺炎链球菌的转化试验肺炎链球菌的转化试验 Department of M
15、icrobiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉接合conjugationn概念：u两个细菌接触，供体菌通过性菌毛将DNA直接转入受体菌内，使受体菌获得新的遗传性状的过程。Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉接合conjugationn通过性菌毛相互连接沟通，将
16、质粒或染色体的DNA从供体菌转移给受体菌nF质粒（fertilityplasmid）u雄性菌（F+）u雌性菌（F-）F F质粒接合转移模式图质粒接合转移模式图Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉高频重组菌株(highfrequencyrecombination,Hfr)n概念uF质粒可整合到细菌染色体上，有可能引起宿主染色体发生高频率的转移，故称为HfrDepartment of Microbiology,
17、 Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉电镜下的接合电镜下的接合F菌菌F 菌菌Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉F质粒的接合质粒的接合nF- 菌菌F+ 菌菌F- 菌菌F+ 菌菌F- 菌菌F+ 菌菌F+ 菌菌F+ 菌菌性菌毛末端性菌毛末端- -受体接合桥形成受体接合桥形成F F
18、质粒形成切口，一条质粒形成切口，一条DNADNA链进入受体菌内链进入受体菌内F F质粒留在供体细胞的一质粒留在供体细胞的一条链进行复制并形成互条链进行复制并形成互补链补链Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉FFFF-vF质粒的接合粒的接合Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbi
19、n Medical University 张文莉张文莉转导transductionn n概概念念：以以噬噬菌菌体体为为媒媒介介，将将供供体体菌菌DNADNA片片段段转转移移到到受受体体菌菌内内，使使受受体体菌获得新的遗传性状。菌获得新的遗传性状。Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉普遍性转导普遍性转导(generalized transduction) n噬菌体转导供体菌染色体上噬菌体转导供体菌染色体上任何
20、部位任何部位DNA片片段段，发生于裂解期。，发生于裂解期。 n 完全转导完全转导u供体菌供体菌DNA片段与受体菌染色体整合并随之传代。片段与受体菌染色体整合并随之传代。 n 流产转导流产转导u供体菌供体菌DNA片段不与受体菌染色体整合也不可自片段不与受体菌染色体整合也不可自我复制我复制 （大多为此）（大多为此）Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉细菌裂解期细菌DNA（将供菌任意DNA装配）噬菌体DNA普遍性
21、转导模式图整合未整合完全转导流产转导细菌被普遍性转导噬菌体感染Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉GeneralizedTransductionDepartment of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉局限性转导局限性转导(restricte
22、dtransduction)36 n前噬菌体从宿主菌染色体上脱离时前噬菌体从宿主菌染色体上脱离时发生偏差发生偏差，将，将前噬菌体前噬菌体两侧的宿主染色体基因转移到受体菌两侧的宿主染色体基因转移到受体菌，使受体菌的遗传性状发生改变的过程使受体菌的遗传性状发生改变的过程n噬菌体转导供体菌染色体上噬菌体转导供体菌染色体上特定部位的特定部位的DNA片段片段, 发生于溶原期发生于溶原期n噬菌体将自身一段噬菌体将自身一段DNA留在供菌染色体上，留在供菌染色体上， 却却将相邻供菌的部分将相邻供菌的部分DNA带给受菌并带给受菌并整合至受体菌整合至受体菌染色体上染色体上Department of Microbi
23、ology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉37 局限性转导模式图局限性转导模式图正常脱离正常脱离断裂和断裂和 再接再接断裂和断裂和 再接再接偏差脱离偏差脱离galgalgalgalbiobiobiobioDepartment of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉转导转导 接合接合 转化转化
24、Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉溶原性转换Lysogenicconversionn溶原性细菌因染色体上整合有前噬菌体而获新遗传性状Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉原生质体融合Protoplastfusionn细菌
25、形成原生质体后，在聚乙二醇作用下可以使两个细菌细胞发生融合n特点u使原来不具有基因转移条件的细菌实现基因转移和重组u可用于同种或异种之间Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉41 概念：概念：人工将两种不同的细菌经溶菌酶人工将两种不同的细菌经溶菌酶 或青霉素等处理，失去细胞壁成为原生或青霉素等处理，失去细胞壁成为原生 质体后进行相互融合的过程质体后进行相互融合的过程 融合剂：融合剂：PEGPEG（聚乙二醇）（
26、聚乙二醇） 应用：应用：基因转输、实验工具基因转输、实验工具5、原生、原生质体融合（体融合（proptopast fusion）41 原生原生质体融合体融合Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉第四节细菌遗传学的应用n在诊断、治疗和预防方面的应用n检测致癌物质n在流行病学方面的应用n在基因工程方面的应用Department of Microbiology, Harbin Medical UniversityD
27、epartment of Microbiology, Harbin Medical University 张文莉张文莉Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉小结n与细菌遗传相关的物质n细菌的变异现象n细菌变异的机理n细菌遗传变异在医学上的应用Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉教学大纲n掌握内容：细菌的遗传物质；基因转移与重组方式的种类及定义；噬菌体及其相关概念。n熟悉内容：细菌的变异类型；噬菌体与宿主菌相互关系。n了解内容：细菌的变异现象；细菌遗传变异研究的实际意义。Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical University 张文莉张文莉问题n简述噬菌体的概念、分类、及主要应用。n细菌基因转移和重组的方式有几种？各自的特点是甚麽？
