Validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.
Validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.
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DOI：
10.1371/journal.pone.0020449
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Lopez-Ribot JL
中科院分区：
文献类型：
--
作者：
Chaturvedi AK;Lazzell AL;Saville SP;Wormley FL Jr;Monteagudo C;Lopez-Ribot JL
了解传染病的发病机理需要检查和成功整合与微生物毒力和宿主反应相关的参数。四环素调控系统作为控制微生物基因表达（包括体内表达）的一种实用而有效的方法，近年来得到了许多研究小组的青睐。然而，四环素类药物（包括强力霉素）的某些免疫调节作用可能会限制其用于评价感染期间宿主反应的用途。在这里，我们已经使用了一个完善的小鼠模型播散性念珠菌病，这是高度依赖于由真菌细胞和宿主的免疫状态显示的毒力，以验证该系统的使用。我们证明了野生型C.白色念珠菌CAF 2 -1菌株不含任何tet-可调节元件，不受多西环素存在的影响。此外，通过多分析物分析确定的关键细胞因子、趋化因子和许多其他生物标志物的水平基本上不受感染期间抗生素存在的影响。我们的研究结果表明，所需的四环素调控启动子基因表达系统的多西环素的水平，在念珠菌感染的全球主机的反应没有检测到的影响。由于tet可调控系统现在越来越多地用于各种病原微生物，这些观察结果在感染性疾病领域具有广泛的意义。
Understanding the pathogenesis of infectious disease requires the examination and successful integration of parameters related to both microbial virulence and host responses. As a practical and powerful method to control microbial gene expression, including in vivo, the tetracycline-regulatable system has recently gained the favor of many investigative groups. However, some immunomodulatory effects of the tetracyclines, including doxycycline, could potentially limit its use to evaluate host responses during infection. Here we have used a well-established murine model of disseminated candidiasis, which is highly dependent on both the virulence displayed by the fungal cells and on the host immune status, to validate the use of this system. We demonstrate that the pathogenesis of the wild type C. albicans CAF2-1 strain, which does not contain any tet-regulatable element, is not affected by the presence of doxycycline. Moreover levels of key cytokines, chemokines and many other biomarkers, as determined by multi-analyte profiling, remain essentially unaltered by the presence of the antibiotic during infection. Our results indicate that the levels of doxycycline needed to control the tetracycline regulatable promoter gene expression system have no detectable effect on global host responses during candidiasis. Because tet-regulatable systems are now being increasingly used in a variety of pathogenic microorganisms, these observations have wide implications in the field of infectious diseases.
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影响因子：
64.5
作者：
Lo, HJ;Kohler, JR;Fink, GR
通讯作者：
Fink, GR
影响因子：
3.4
作者：
Dunston, Christopher R.;Griffiths, Helen R.;Lambert, Peter A.;Staddon, Susan;Vernallis, Ann B.
通讯作者：
Vernallis, Ann B.
影响因子：
12.3
作者：
Odds FC;Gow NA;Brown AJ
通讯作者：
Brown AJ
影响因子：
5
作者：
D'Agostino, P;Arcoleo, F;Cillari, E
通讯作者：
Cillari, E
影响因子：
3.1
作者：
Nakayama, H;Mio, T;Aoki, Y
通讯作者：
Aoki, Y