Use of the common marmoset to study Burkholderia mallei infection.
Use of the common marmoset to study Burkholderia mallei infection.
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DOI：
10.1371/journal.pone.0124181
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lafontaine ER
中科院分区：
文献类型：
--
作者：
Jelesijevic T;Zimmerman SM;Harvey SB;Mead DG;Shaffer TL;Estes DM;Michel F;Quinn FD;Hogan RJ;Lafontaine ER
马氏伯克霍尔德氏菌是一种适应宿主的细菌，在马宿主之外不会持续存在。这种生物引起人畜共患病，在亚洲、非洲、中东和南美洲流行。马氏芽孢杆菌感染通常通过呼吸道或经皮途径发生，最常见的表现是危及生命的肺炎和菌血症。腺体炎很难诊断，需要长时间的抗生素治疗，成功率低。目前还没有预防马氏芽孢杆菌的疫苗，人们担心它会被用作生物威胁剂。因此，我们通过实验建立了非人类灵长类动物鼻内感染模型，以研究该生物并制定对策。对各组猕猴（狐猴）鼻内接种马利梭菌ATCC 23344菌株，监测临床症状长达13天。我们发现，接种2.5 X 104至2.5 X 105细菌剂量的狨猴中，83%在3-4天内发生急性致死感染。疾病的症状很严重，包括嗜睡、食欲不振、结膜炎、粘液化脓性和出血性鼻分泌物，以及在提腹时呼吸困难增加。从这些动物的肺、脾和肝脏中培养mallei伯克霍尔德菌，组织病理检查显示具有腺体特征的病变。挑战实验还显示，91%的动物感染剂量为25至2.5 X 103的细菌，表现出轻微的非特异性疾病症状，培养阴性。一只接种了2.5 X 103种微生物的狨猴出现了中度疾病症状，并在感染后8天达到了人类终点。该制剂在该动物的肝脏和脾脏定殖，组织病理分析显示鼻腔、脾脏和肝脏病变。综上所述，这些数据表明狨猴是研究马尔氏杆菌呼吸道感染的合适模型。
Burkholderia mallei is a host-adapted bacterium that does not persist outside of its equine reservoir. The organism causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by B. mallei typically occurs via the respiratory or percutaneous route, and the most common manifestations are life-threatening pneumonia and bacteremia. Glanders is difficult to diagnose and requires prolonged antibiotic therapy with low success rates. There is no vaccine to protect against B. mallei and there is concern regarding its use as a biothreat agent. Thus, experiments were performed to establish a non-human primate model of intranasal infection to study the organism and develop countermeasures. Groups of marmosets (Callithrix jacchus) were inoculated intranasally with B. mallei strain ATCC 23344 and monitored for clinical signs of illness for up to 13 days. We discovered that 83% of marmosets inoculated with doses of 2.5 X 104 to 2.5 X 105 bacteria developed acute lethal infection within 3–4 days. Signs of disease were severe and included lethargy, inappetence, conjunctivitis, mucopurulent and hemorrhagic nasal discharges, and increased respiratory effort with abdominal lifts. Burkholderia mallei was cultured from the lungs, spleen and liver of these animals, and pathologic examination of tissues revealed lesions characteristic of glanders. Challenge experiments also revealed that 91% of animals infected with doses ranging from 25 to 2.5 X 103 bacteria exhibited mild non-specific signs of illness and were culture negative. One marmoset inoculated with 2.5 X 103 organisms developed moderate signs of disease and reached humane end-points 8 days post-infection. The liver and spleen of this animal were colonized with the agent and pathological analysis of tissues showed nasal, splenic and hepatic lesions. Taken together, these data indicate that the marmoset is a suitable model to study respiratory infection by B. mallei.
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