肺炎链球菌

肺炎链球菌于1881年首次由巴斯德（Louis Pasteur）及G. M. Sternberg分别在法国及美国从患者痰液中分离出。为革兰染色阳性，菌体似矛头状，成双或成短链状排列的双球菌，有毒株菌体外有化学成分为多糖的荚膜。5%～10%正常人上呼吸道中携带此菌。有毒株是引起人类疾病的重要病原菌。

在化脓性球菌中，肺炎链球菌的致病力仅次于金黄色葡萄球菌。不同的是，到目前为止，肺炎链球菌极少对青霉素类抗生素产生耐药性。肺炎球菌主要的致病物质是肺炎球菌溶血素及荚膜。荚膜具有抗原性，是肺炎链球菌分型的依据。此菌可引起大叶性肺炎、脑膜炎、支气管炎等疾病。

生物学性状编辑

肺炎链球菌电镜下的形态

⒈菌体呈矛头状，多成双排列，宽端相对，尖端相背，有较厚荚膜，革兰阳性.

⒉培养特性和生化反应 营养要求及在血平板上菌落特征基本同甲型链球菌，培养时间稍久菌落中央下陷呈脐窝状.在血清肉汤中培养稍久亦因细菌自溶而使混浊的培养液渐变澄清.自溶酶可被胆汁或胆盐等物质活化，加速细菌溶解，故可用胆汁溶菌试验与甲型链球菌相区别；肺炎链球菌能分解菊糖这点也可作为与甲型链球菌相区别的依据.

⒊抗原结构与分型

⑴荚膜多糖抗原 按此抗原不同分为84个血清型，个别型还可分成不同的亚型.其中有20多个型可引起疾病.

⑵菌体抗原

1)C多糖 存在于细胞壁中，为各型肺炎链球菌所共有，可与血清中一种正常蛋白质（C反应蛋白)出现沉淀反应.C反应蛋白（CRP）在急性炎症患者中含量剧增.可用C多糖测定CRP，辅助诊断活动性风湿热等疾病.

2)M蛋白：具有型特异性，类似A群链球菌的M蛋白，但与菌的毒力无关.

病性与免疫性

⒈致病物质 有荚膜，肺炎链球菌溶素O，脂磷壁酸和神经氨酸酶等.

⒉所致疾病 主要引起大叶性肺炎，成人中75%由1,2,3,4,5,7,8,9,12型引起，半数以上为1,2,3型.3型产生大量荚膜物质，毒力强，病死率高.儿童以第6,14,19及23型肺炎链球菌感染最常见.可继发胸膜炎，脓胸，中耳炎，脑膜炎和败血症等.

肺炎链球菌在正常人的口腔及鼻咽部经常存在，一般不致病，只形成带菌状态.只有在免疫力下降时才致病.尤其在呼吸道病毒感染后或婴幼儿，年老体弱者易发生肺部感染.

感染后，可建立较牢固的型特异性免疫.其免疫机制主要是产生荚膜多糖型特异抗体，起调理作用，增强吞噬功

能.

细菌的传播与致病编辑

引起肺炎等疾病的链球菌属细菌。呈圆形，在痰和脓液中常形成短链状，无鞭毛；在人和动物体内可产生荚膜。 该菌对温度抵抗力较弱，在52～56℃时加热15～20分钟即被杀死；对干燥的抵抗力较强，在阴暗处的干痰中可生存1～2月。这种细菌在自然界中分布 广泛，常生活在正常人的鼻腔中，多数不致病或致病力很弱，少数致病力较强。其能否致病与荚膜有密切关系，因荚膜能抵抗人体内吞噬细胞的吞噬作用而大量繁殖，引起疾病。肺炎链球菌主要引起大叶性肺炎以及气管炎、中耳炎、脑膜炎、胸膜炎、心内膜炎、败血症等疾病。典型的大叶性肺炎起病急骤，病人有高烧、寒颤，开始时有阵发性干咳，不久有少量粘液痰，随后痰变黄色，呈粘脓性。病人在发热期间，应卧床休息，吃容易消化的食物，多喝水。一般病程1～2周预防。用细菌荚膜多糖制备的多糖疫苗进行预防，效果较好。磺胺类药物、青霉素等对肺炎等疾病的治疗较为有效。

由肺炎链球菌引起的急性肺部感染叫肺炎链球菌肺炎。该菌革兰染色阳性，常为短链状，细菌外面由多糖体组成的荚膜为致病的物质基础。若3岁以下的婴幼儿肺部受到感染，则引起支气管肺炎；3岁以上年长儿受到感染，由于此时机体抵抗力逐渐增强，能使病变局限于一个肺叶或一个节段，以右上叶或左下叶最为多见，故肺炎链球菌肺炎又叫大叶性肺炎，近年来发病率较低。

起病多急骤（少数患儿先有轻微的上呼吸道感染症状），中毒症状重。突然高热、体温可达40℃～41℃，头痛、胸痛、呼吸急促，烦躁不安，早期往往不咳嗽或轻咳，病儿常不吐痰。年长儿可有寒战、咯吐铁锈色痰，但有的患儿仍咳黄脓痰。重症患儿可有惊厥、谵妄及昏迷等中毒性脑病表现。

5细菌的生物学特性编辑

典型的肺炎链球菌为革兰染色阳性球菌，直径约1μm。常呈双排列。菌体成矛头状，宽端相对，尖端向外。在痰、脓液标本中可呈单个或短链状。有毒株在体内形成荚膜。普通染色时荚膜不着色，表现为菌体周围透明环。无鞭毛。不形成芽胞。菌体衰老时，或由于自溶酶（autolysin）的产生将细菌裂解后，可呈现革兰染色阴性。

肺炎链球菌 荚膜染色&amp

本菌营养要求较高，需在含血液或血清的培养基中生长。在固体培养基上形成小圆形、隆起、表面光滑、湿润的菌落。培养初期菌落隆起呈穹窿形，随着培养时间延长，细菌产生的自溶酶裂解细菌，使菌落中央凹陷，边缘隆起成“脐状”。表面活性剂如胆汁或脱氧胆酸盐可激活自溶酶，加速菌体自溶。

兼性厌氧，C02 5-10%生长最好，且生成的菌落周围有草绿色溶血环。若于液体培养基中培养24h，呈均匀混浊，后期可因产生自溶而变得澄清。

甲型溶血性链球菌不产生自溶酶，故加入胆盐等表面活性剂不能溶解，利用此特点可鉴别甲型溶血性链球菌与肺炎链球菌。肺炎链球菌在血琼脂平板上菌落周围形成α溶血环。细菌生长的能量来源于分解葡萄糖，伴随乳酸的形成。乳酸的堆积会抑制细菌的生长，故间断性加入碱可使肺炎链球菌大量繁殖。Optochin可抑制肺炎链球菌生长。

该菌可分解多种糖类，产酸不产气。胆汁溶解试验阳性、Optochin敏感试验阳性。

大多数新分离出的肺炎链球菌可发酵菊糖，故菊糖发酵试验在鉴别肺炎球菌与甲型溶血性链球菌时有一定的参

考价值。

抗原构造、分型及变异编辑

荚膜多糖抗原

存在于肺炎链球菌荚膜中。根据荚膜多糖抗原性的不同将肺炎球菌分为91个血清型。

菌体抗原

⑴C多糖：存在于肺炎链球菌细胞壁中，具有种特异性，为各型菌株所共有。C多糖可被血清中C-反应蛋白沉淀。在钙离子存在时，C多糖可与正常人血清中称为C-反应蛋白（C reactive protein,CRP）的β球蛋白结合，发生沉淀。

⑵M蛋白：具有型特异性。M蛋白刺激机体产生的相应抗体无保护作用。

变异

肺炎链球菌可能发生的变异有荚膜变异：即从有荚膜有毒力的光滑（S）型菌变异为失去荚膜毒力减低或消失的粗糙（R）型。

抵抗力

抵抗力较弱，56℃15～30分钟即被杀死。对一般消毒剂敏感。有荚膜株抗干燥力较强。对青霉素、红霉素、林可霉素等敏感。

致病性编辑

致病物质

1．荚膜（capsule) 是肺炎链球菌主要的致病因素。无荚膜的变异株无毒力，感染实验动物，如鼠、兔等，很快被吞噬细胞吞噬并杀灭。有荚膜的肺炎球菌可抵抗吞噬细胞的吞噬，有利于细菌在宿主体内定居并繁殖。

2．肺炎链球菌溶血素（pneumolysin) 高浓度时对实验动物有致死性。对人的致病机理尚待确定。

3．紫癜形成因子（purpura-producing principle) 注入家兔皮内，可产生紫癜及出血点并伴有内脏出血。紫癜形成因子与人类肺炎球菌感染间的关系尚不明确。

所致疾病

肺 炎链球主要引起人类大叶性肺炎。75%的成年人肺炎链球菌肺炎及50%以上严重的肺炎链球菌菌血症是由1～8型肺炎链球菌引起。肺炎链球菌6、14、19 及23型，常引起儿童肺炎链球菌性疾病。40%～70%的正常人上呼吸道中携带有毒力的肺炎链球菌。由此可见呼吸道粘膜对肺炎链球菌存在很强的自然抵抗 力。当出现某种降低这种抵抗功能的因素时，肺炎链球菌可引起感染，如①呼吸道功能异常：病毒及其它感染性因子损伤呼吸道粘膜上皮细胞； 某些异常因素（如过敏）导致粘液的过度分泌，使侵入的病原菌受到保护；各种原因导致的支气管阻塞及各种原因导致的纤毛功能损伤；②酒精及药物中毒：酒精及 某些药物中毒可抑制吞噬细胞的活性及咳嗽反射，有利于病原菌的吸入；③循环系统功能异常及任何原因导致的肺充血、心功能衰竭；④其它：营养缺陷、体质虚 弱、贫血、血清补体水平低下等。肺炎链球菌肺炎常突然发病，表现为高热、寒战、胸膜剧烈疼痛、咳铁锈色痰。10%～20%的患者可于高热期伴发菌血症。其病理表现主要是最初肺泡内有大量纤维蛋白渗出液，继之是红细胞和白细胞向肺泡内渗出，最终导致病变部位肺组织实变。病变通常仅累及单个肺叶，故称为大叶性肺炎。如果早期使用抗生素治疗，可阻止肺实变发生。

肺炎链球菌也可侵入机体其它部位，引起继发性胸膜炎、中耳炎、乳突炎、心内膜炎及化脓性脑膜炎等。

9免疫性

肺炎链球菌感染后，机体可建立较牢固的型特异性免疫，同型病菌的再次感染少见。患者发病后5～6天，体内可形成荚膜多糖型特异性抗体。这种抗体与荚膜结合后，肺炎链球菌易被机体吞噬细胞吞噬杀灭。补体在清除病原菌过程中发挥调理作用，当抗原抗体复合物与补体结合后，可增强吞噬细胞对病原菌的吞噬功能。

细菌的防治

肺炎链球菌感染关键在于养成良好的卫生习惯，保持环境卫生。必要时对体弱儿童及老年人可用疫苗进行预防注射，如用细菌荚膜多糖制备的多糖疫苗进行预防，效果较好。

病人在发热期间，应卧床休息，吃容易消化的食物，多喝水。磺胺类药物、青霉素等对肺炎等疾病的治疗较为有效。

由于肺炎球菌对多种抗生素敏感，早期治疗通常患者可很快恢复。青霉素G为首选治疗药物。但已发现肺炎球菌对青霉素、红霉素、四环素的耐药菌株。对青霉素的耐药菌株，对万古霉素依然敏感。

肺部查体

肺部早期往往缺乏明显阳性体征，或仅有呼吸音减低，晚期才出现肺实变体征，如胸部叩诊呈浊音，可闻及管状呼吸音及大量的湿罗音。

血常规

白细胞总数及中性粒细胞均升高。

痰培养

可见肺炎链球菌生长。

X线检查

沿肺叶分布大片状模糊阴影，密度均匀，边缘清楚，占全肺叶或一个节段。

http://en.wikipedia.org/wiki/Streptococcus_pneumoniae

Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, alpha-hemolytic, facultative anaerobic member of the genus Streptococcus.^[1] A significant human pathogenic bacterium, S. pneumoniae was recognized as a major cause of pneumonia in the late 19th century, and is the subject of many humoral immunity studies.

S. pneumoniae resides asymptomatically in the nasopharynx of healthy carriers. The respiratory tract, sinuses, and nasal cavity are the parts of host body that are usually infected. However, in susceptible individuals, such as elderly and immunocompromised people and children, the bacterium may become pathogenic, spread to other locations and cause disease. S. pneumoniae is the main cause of community acquired pneumonia and meningitis in children and the elderly, and of septicemia in HIV-infected persons. The methods of transmission include sneezing, coughing, and direct contact with an infected person.

Despite the name, the organism causes many types of pneumococcal infections other than pneumonia. These invasive pneumococcal diseases include bronchitis, rhinitis, acute sinusitis, otitis media, conjunctivitis, meningitis, bacteremia, sepsis, osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, cellulitis, and brain abscess.^[2]

S. pneumoniae is one of the most common causes of bacterial meningitis in adults and young adults, along with Neisseria meningitidis, and is the leading cause of bacterial meningitis in adults in the USA. It is also one of the top two isolates found in ear infection, otitis media.^[3] Pneumococcal pneumonia is more common in the very young and the very old. It also is a major bacterium for invasive diseases like pneumonia and meningitis in South Asian children 12 years of age, though the evidence is of low quality and scarce.^[4]

S. pneumoniae can be differentiated from Streptococcus viridans, some of which are also alpha-hemolytic, using an optochin test, as S. pneumoniae is optochin-sensitive. S. pneumoniae can also be distinguished based on its sensitivity to lysis by bile, the so-called "bile solubility test". The encapsulated, Gram-positive coccoid bacteria have a distinctive morphology on Gram stain, lancet-shaped diplococci. They have a polysaccharide capsule that acts as a virulence factor for the organism; more than 90 different serotypes are known, and these types differ in virulence, prevalence, and extent of drug resistance.

Contents

• 1 History
• 2 Genetics
• 3 Transformation in S. pneumoniae
• 4 Infection
• 5 Vaccine
• 6 Interaction with Haemophilus influenzae
• 7 Diagnosis
• 8 See also
• 9 References
• 10 External links

History

In 1881, the organism, known as the pneumococcus for its role as an [etiologic agent] of pneumonia, was first isolated simultaneously and independently by the U.S. Army physician George Sternberg^[5] and the French chemist Louis Pasteur.^[6]

The organism was termed Diplococcus pneumoniae from 1920^[7] because of its characteristic appearance in Gram-stained sputum. It was renamed Streptococcus pneumoniae in 1974 because of its growth in chains in liquid growth media.

S. pneumoniae played a central role in demonstrating genetic material consists of DNA. In 1928, Frederick Griffith demonstrated transformation of life, turning harmless pneumococcus into a lethal form by co-inoculating the live pneumococci into a mouse along with heat-killed, virulent pneumococci.^[8] In 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty demonstrated the transforming factor in Griffith‘s experiment was DNA, not protein, as was widely believed at the time.^[9] Avery‘s work marked the birth of the molecular era of genetics.^[10]

Genetics

The genome of S. pneumoniae is a closed, circular DNA structure that contains between 2.0 and 2.1 million base pairs, depending on the strain. It has a core set of 1553 genes, plus 154 genes in its virulome, which contribute to virulence, and 176 genes that maintain a noninvasive phenotype. Genetic information can vary up to 10% between strains.^[11]

Transformation in S. pneumoniae

Natural bacterial transformation involves the transfer of DNA from one bacterium to another through the surrounding medium. Transformation is a complex, developmental process requiring energy, dependent on expression of numerous genes. In S. pneumoniae at least 23 genes are required. In order for a bacterium to bind, take up and recombine exogenous DNA into its chromosome it must enter a special physiological state, called competence.

Competence, in S. pneumoniae, is induced by DNA-damaging agents such as mitomycin C, a DNA inter-strand cross-linking agent, and the fluoroquinolone antibiotics norfloxacin, levofloxacin and moxifloxacin, topoisomerase inhibitors that cause double-strand breaks.^[12] Transformation protects S. pneumoniae against the bactericidal effect of mitomycin C.^[13] Michod et al.^[14] summarized evidence that induction of competence in S. pneumoniae is associated with increased resistance to oxidative stress and increased expression of the RecA protein, a key component of the recombinational repair machinery for removing DNA damages. On the basis of these findings, they suggested that transformation is an adaptation for repairing oxidative DNA damages. S. pneumoniae infection stimulates polymorphonuclear leukocytes (granulocyte) to produce an oxidative burst that is potentially lethal to the bacteria. The ability of S. pneumoniae to repair the oxidative DNA damages in its genome, caused by this host defense, likely contributes to this pathogen’s virulence.

Infection

Main article: Pneumococcal infection

S. pneumoniae is part of the normal upper respiratory tract flora, but, as with many natural flora, it can become pathogenic under the right conditions, like if the immune system of the host is suppressed. Invasins, such as pneumolysin, an anti-phagocytic capsule, various adhesins and immunogenic cell wall components are all major virulence factors.

Vaccine

Main article: Pneumococcal vaccine

Interaction with Haemophilus influenzae

Both Haemophilus influenzae (H. influenzae) and S. pneumoniae can be found in the human upper respiratory system. A study of competition in vitro revealed S. pneumoniae overpowered H. influenzae by attacking it with hydrogen peroxide.^[15]

When both bacteria are placed together into the nasal cavity of a mouse, within 2 weeks, only H. influenzae survives. When both are placed separately into a nasal cavity, each one survives. Upon examining the upper respiratory tissue from mice exposed to both bacteria, an extraordinarily large number of neutrophil immune cells were found. In mice exposed to only one bacterium, the cells were not present.

Lab tests show neutrophils that were exposed to already-dead H. influenzae were more aggressive in attacking S. pneumoniae than unexposed neutrophils. Exposure to killed H. influenzae had no effect on live H. influenzae.

Two scenarios may be responsible for this response:

1. When H. influenzae is attacked by S. pneumoniae, it signals the immune system to attack the S. pneumoniae
2. The combination of the two species sets off an immune system alarm that is not set off by either species individually.

It is unclear why H. influenzae is not affected by the immune system response.^[16]

Diagnosis

Diagnosis is generally made based on clinical suspicion along with a positive culture from a sample from virtually any place in the body. An ASO Titre of >200 units is significant.^[2] S. pneumoniae is, in general, optochin sensitive, although optochin resistance has been observed.^[17]

Atromentin and leucomelone possess antibacterial activity, inhibiting the enzyme enoyl-acyl carrier protein reductase, (essential for the biosynthesis of fatty acids) in S. pneumoniae.^[18]