The role of resuscitation promoting factors in pathogenesis and reactivation of Mycobacterium tuberculosis during intra-peritoneal infection in mice.
The role of resuscitation promoting factors in pathogenesis and reactivation of Mycobacterium tuberculosis during intra-peritoneal infection in mice.
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DOI：
10.1186/1471-2334-7-146
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发表时间：
2007-12-17
影响因子：
3.7
通讯作者：
Kaprelyants, Arseny
中科院分区：
文献类型：
--
作者：
Biketov, Sergey;Potapov, Vasilii;Ganina, Elena;Downing, Katrina;Kana, Bavesh D.;Kaprelyants, Arseny
结核分枝杆菌可以进入休眠状态，这导致世界上三分之一的人口感染潜伏性结核病，使得对潜伏和再激活的研究至关重要。M.结核杆菌编码五种复苏促进因子（Rpfs），其与先前参与体外休眠细菌再活化的溶菌酶样酶具有很强的相似性。我们已经开发了一种具有免疫调节的小鼠腹膜内感染模型，该模型在小鼠肺中具有与在鼠气溶胶感染模型中观察到的那些相似的特性。我们已经在我们的腹腔模型中评估了缺少两个或三个rpf基因的突变体在不同组合中的行为。用H37Rv野生型M.结核病或突变株缺乏两个或三个rpf基因的不同组合。感染90天后给予氨基胍（AG）或抗TNF α抗体。在感染后的不同时间间隔，通过接种器官匀浆的系列稀释液并计数细菌来测定器官细菌负荷。我们发现，腹腔内给药后，检测的rpf三重和双突变体向小鼠肺部扩散的能力减弱，并且在氨基胍和抗TNF α抗体诱导的免疫抑制后，其重新生长的能力存在缺陷。Rpf蛋白可能对慢性TB感染的发展及其体内再活化具有重要的生理作用。
Mycobacterium tuberculosis can enter into a dormant state which has resulted in one third of the world's population being infected with latent tuberculosis making the study of latency and reactivation of utmost importance. M. tuberculosis encodes five resuscitation promoting factors (Rpfs) that bear strong similarity to a lysozyme-like enzyme previously implicated in reactivation of dormant bacteria in vitro. We have developed an intraperitoneal infection model in mice, with immune modulation, that models chronic infection with similar properties in mouse lungs as those observed in the murine aerosol infection model. We have assessed the behavior of mutants that lack two or three rpf genes in different combinations in our intraperitoneal model. C57Bl/6 mice were intraperitonealy infected with H37Rv wild type M. tuberculosis or mutant strains that lacked two or three rpf genes in different combinations. After 90 days of infection aminoguanidine (AG) or anti-TNFα antibodies were administrated. Organ bacillary loads were determined at various intervals post infection by plating serial dilutions of organ homogenates and enumerating bacteria. We found that the rpf triple and double mutants tested were attenuated in their ability to disseminate to mouse lungs after intraperitoneal administration and were defective in their ability to re-grow after immunosuppression induced by administration of aminoguanidine and anti-TNFα antibodies. Rpf proteins may have a significant physiological role for development of chronic TB infection and its reactivation in vivo.
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DOI：
10.1084/jem.123.3.469
发表时间：
1966-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
McCune RM;Feldmann FM;McDermott W
通讯作者：
McDermott W
影响因子：
3.1
作者：
Downing, KJ;Mischenko, VV;Mizrahi, V
通讯作者：
Mizrahi, V
影响因子：
120.7
作者：
Dye, C;Scheele, S;Raviglione, RC
通讯作者：
Raviglione, RC
影响因子：
3.1
作者：
Mohan, VP;Scanga, CA;Chan, J
通讯作者：
Chan, J
影响因子：
3.6
作者：
Senaratne, RH;De Silva, AD;Riley, LW
通讯作者：
Riley, LW