validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease验证四环素regulatable基因表达系统的传染病的发病机制的研究.pdfVIP

Validation of the Tetracycline Regulatable Gene Expression System for the Study of the Pathogenesis of Infectious Disease 1 1 1 1 2 Ashok K. Chaturvedi , Anna L. Lazzell , Stephen P. Saville , Floyd L. Wormley Jr. Carlos Monteagudo , Jose L. Lopez-Ribot1* 1 Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, Texas, United States of America, 2 Departmento de ´ ´ Patologıa, Facultad de Medicina y Odontologıa, Universidad de Valencia, Valencia, Spain Abstract 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 pres