第11章-分枝杆菌属课件.ppt
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1、第十三章第十三章 分枝杆菌属分枝杆菌属(Mycobacterium)第一节第一节 结核分枝杆菌结核分枝杆菌第二节第二节 麻风分枝杆菌麻风分枝杆菌第三节第三节 其他分支杆菌其他分支杆菌A 22-year-old gravid African-American woman was evaluated at 23 weeks gestation during her second pregnancy because of a positive tuberculin skin test result with 18 mm of induration.The patient reported a his
2、tory of dry cough and fever for 2 months,and weight loss and night sweats for 1 month.She denied hemoptysis.The findings of her physical examination were unremarkable except for a body weight of 48 kg(body mass index,18.3 kg/m2).On examination,her temperature was 42C.Breath sounds were normal,and th
3、ere were no crackles,rales,or rhonchi.The patient was admitted to the hospital.The chest radiograph revealed a left upper lung cavity(Fig 1).Additional infiltrates could be seen in the entire left lung and in the right parahilar mid-lung field.Several concentrated sputum samples revealed numerous ac
4、id-fast bacilli.Daily antituberculous therapy was initiated with rifampin,600 mg,isoniazid,300 mg,and ethambutol,700 mg(with a target of 15 mg/kg).One smear-positive specimen was immediately processed for susceptibility testing after communicating with the mycobacteriology laboratory.After 3 weeks o
5、f treatment,the patient continued to have a temperature of up to 39.4C and experienced a weight loss of about 5 kg.A repeat chest radiograph revealed a worsening of the left lung infiltrate and a persistence of the right-sided infiltrate.Fig 1 Initial chest radiograph of a pregnant woman 分枝杆菌属分枝杆菌属(
6、Mycobacterium):是一类细长略弯曲的杆菌,因繁殖时有分枝是一类细长略弯曲的杆菌,因繁殖时有分枝生长趋势而得名。生长趋势而得名。Scientific classificationKingdom:BacteriaPhylum:ActinobacteriaOrder:ActinomycetalesSuborder:CorynebacterineaeFamily:MycobacteriaceaeGenus:MycobacteriumThe classification-based upon cladistics 1 Slowly growing 1.1 Mycobacterium tube
7、rculosis complex (MTBC)members are causative agents of human and animal tuberculosis.1.2 Mycobacterium avium complex(MAC),is a group of species which,in a disseminated infection but not lung infection,used to be a significant cause of death in AIDS patients.1.3 Mycobacterium gordonae clade 1.4 Mycob
8、acterium kansasii clade 1.5 Mycobacterium nonchromogenicum/terrae clade 1.6 Mycolactone-producing mycobacteria M.ulcerans,which causes the Buruli,or Bairnsdale,ulcer 1.7 Mycobacterium simiae clade 1.8 Ungrouped M.leprae,which causes leprosy 2 Intermediate growth rate 3 Rapidly growing 4 Ungrouped My
9、cobacterium tuberculosis complex(MTBC)members are causative agents of human and animal tuberculosis.Species in this complex include:M.tuberculosis,the major cause of human tuberculosis M.bovis M.bovis BCG M.africanum M.canetti M.caprae M.microti M.pinnipedii 特点特点:细胞壁含有大量的脂类菌体不易着色,但加温或延长染色时间着色后能抵抗盐酸乙
10、醇的脱色,故采用抗酸染色,故又称抗酸杆菌(acid-fast bacilli)无特殊结构,致病与菌体成分有关,形成慢性肉芽肿性病变营养要求高,生长缓慢可分为三大类:结核分枝杆菌 麻风分枝杆菌 非结核分枝杆菌(非典型分枝杆菌)第一节第一节 结核分枝杆菌结核分枝杆菌结核分枝杆菌结核分枝杆菌(M.tuberculosis)俗称结核杆菌俗称结核杆菌(tubercle bacilli):为为结核病结核病的病原体。的病原体。Tuberculosis comes from the Latin word,tuberculum,meaning protuberance,projection or growth,
11、and refers to the tumor-like nodules that victims often display.In fact,until TBs bacterial agent was discovered in 1882,many physicians thought TBs characteristic nodules and wasting identified it as a form of cancer.Robert Koch(1843-1910)Tuberculosis incidence rate,2004.Multi-drug resistant tuberc
12、ulosis,2004 distribution of proportion of MDR-TB among new TB cases,1994-2009/WHO Tuberculosis(TB)is the worlds leading infectious killer of young and middle-aged adults,causing 26 percent of avoidable deaths in the developing world.The Global Burden of Disease study places TB among the seven leadin
13、g causes of lost Disability-Adjusted Life Years(DALYs)well into the 21st century.-International Food Policy Research Institute 一、生物学性状一、生物学性状 形态染色形态染色菌体细长微弯,有时呈分枝状菌体细长微弯,有时呈分枝状排列不规则,多单个散在排列不规则,多单个散在无特殊结构无特殊结构抗酸染色阳性抗酸染色阳性L L型抗酸染色阴性而革兰染色阳性型抗酸染色阴性而革兰染色阳性 培养特性培养特性 专性需氧,温度专性需氧,温度37,pH偏酸偏酸6.56.8 营养要求高,罗氏营
14、养要求高,罗氏(Lowenstein)培养基(蛋黄、甘培养基(蛋黄、甘油、天门冬素、马铃薯、无机盐、孔雀绿等)油、天门冬素、马铃薯、无机盐、孔雀绿等)生长缓慢,生长缓慢,18h分裂一次,分裂一次,24W形成形成R型菌落,型菌落,“菜花样菌落菜花样菌落”,乳白色干燥不透明,表面呈颗,乳白色干燥不透明,表面呈颗粒结节,边缘不整齐粒结节,边缘不整齐 生化反应生化反应 不发酵糖类不发酵糖类 触酶试验阳性触酶试验阳性 热触酶试验阴性热触酶试验阴性 抵抗力强抵抗力强 抗干燥,抗酸碱,抗化学消毒剂;抗干燥,抗酸碱,抗化学消毒剂;对湿热和紫外线敏感;对湿热和紫外线敏感;对抗结核药(异烟肼、利福平、环丝氨酸对抗
15、结核药(异烟肼、利福平、环丝氨酸、乙胺丁醇等)敏、乙胺丁醇等)敏感,但易产生耐药性。感,但易产生耐药性。变异性:变异性:结核杆菌多种性状可发生变异结核杆菌多种性状可发生变异 形态变异:在异烟肼、溶菌酶等作用下形成形态变异:在异烟肼、溶菌酶等作用下形成L型(多形性);型(多形性);菌落变异:菌落变异:R-S型变异,性状典型型变异,性状典型不典型,毒力减弱;不典型,毒力减弱;毒力变异:卡介苗(毒力变异:卡介苗(Bacilli Calmette-Guerin,BCG):):1908年两位科学家将有毒的年两位科学家将有毒的牛型分枝杆菌牛型分枝杆菌接种在含甘油、接种在含甘油、胆汁、马铃薯的培养基中,经胆
16、汁、马铃薯的培养基中,经13年年230代传代获得的减毒菌代传代获得的减毒菌株,即卡介苗沿用至今;株,即卡介苗沿用至今;耐药菌株。耐药菌株。1:NASTA M.The appearance of L forms in a Mycobacterium(Myco.phlei)Article in French.Rev Sci Med.1962;7:83-6.二、致病性和免疫性二、致病性和免疫性 结核杆菌无侵袭性酶,不含内毒素也结核杆菌无侵袭性酶,不含内毒素也不产生外毒素,其致病性主要由于不产生外毒素,其致病性主要由于:菌体成分菌体成分 细菌繁殖引起炎症细菌繁殖引起炎症 代谢产物毒性作用代谢产物毒性作
17、用 抗体对菌体成分产生免疫病理损伤抗体对菌体成分产生免疫病理损伤致病物质致病物质-菌体成分菌体成分 脂质脂质-存在细胞壁,存在细胞壁,占细胞壁干重的占细胞壁干重的60%,含含量与毒力平行,包括磷脂、脂肪酸和蜡质:量与毒力平行,包括磷脂、脂肪酸和蜡质:索状因子索状因子(cord factor)(糖脂(糖脂分枝菌酸分枝菌酸+海藻糖)海藻糖)磷脂磷脂 蜡质蜡质D(分枝菌酸(分枝菌酸+肽糖脂)肽糖脂)硫酸脑苷脂硫酸脑苷脂作用:引起结核结节,慢性肉芽肿及组织细作用:引起结核结节,慢性肉芽肿及组织细胞干酪样坏死等病变。胞干酪样坏死等病变。海藻糖海藻糖(Trehalose)Mycolic acids the
18、 side chains(R1 and R2)vary in length according to the genus;C60 to C90 in Mycobacterium;C40 to C56 in Nocardia.The function of mycolic acids:Increase resistance to chemical damage and dehydration,Prevent the effective activity of hydrophobic antibiotics,Allow the bacterium to grow readily inside ma
19、crophages,effectively hiding it from the hosts immune system.Cord Factor 毒力成分毒力成分组成组成作用作用索状因子索状因子(cord factor)糖脂糖脂分枝菌酸分枝菌酸+海藻糖海藻糖破坏线粒体膜,影响呼吸,破坏线粒体膜,影响呼吸,抑制白细胞游走引起慢性肉抑制白细胞游走引起慢性肉芽肿芽肿磷脂磷脂刺激单核细胞增生,病灶结刺激单核细胞增生,病灶结核结节和干酪样坏死核结节和干酪样坏死蜡质蜡质D(wax-D)分枝菌酸分枝菌酸+肽糖脂肽糖脂引起动物迟发型超敏反应,引起动物迟发型超敏反应,具免疫佐剂作用具免疫佐剂作用硫酸脑苷脂硫酸脑
20、苷脂抑制吞噬体与溶酶体的融合抑制吞噬体与溶酶体的融合毒力成分及其作用毒力成分及其作用致病物质致病物质-菌体成分菌体成分 蛋白质蛋白质 有抗原性、本身无毒,如结核菌素有抗原性、本身无毒,如结核菌素 蛋白质蛋白质+蜡质蜡质D-迟发型变态反应迟发型变态反应 组织坏死、全身中毒症状组织坏死、全身中毒症状 结核结节形成结核结节形成 分枝菌生长素(分枝菌生长素(mycobactin)可溶性铁螯合物可溶性铁螯合物 多糖多糖Mycobactin:a substance in some mycobacteria capable of promoting the growth of other mycobacte
21、ria;it is capable of extracting ferric ion from the medium which some Mycobacterium spp.are unable to do.所致疾病所致疾病传染源:开放性肺结核病人痰传染源:开放性肺结核病人痰传播途径:呼吸道、消化道、皮肤黏膜传播途径:呼吸道、消化道、皮肤黏膜所致疾病所致疾病 肺部感染肺部感染(1 1)原发感染)原发感染常见儿童(外源性感染)常见儿童(外源性感染)结局结局机体抵抗力强机体抵抗力强 形成结核结节形成结核结节纤维化纤维化钙化钙化自愈自愈(但病灶内常有细菌的潜伏)(但病灶内常有细菌的潜伏)机体抵抗力
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