0000000000394665
AUTHOR
Ashok K. Chaturvedi
Validation of the Tetracycline Regulatable Gene Expression System for the Study of the Pathogenesis of Infectious Disease
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 im…
Physiologic Expression of the Candida albicans Pescadillo Homolog Is Required for Virulence in a Murine Model of Hematogenously Disseminated Candidiasis
ABSTRACT Morphogenetic conversions contribute to the pathogenesis of Candida albicans invasive infections. Many studies to date have convincingly demonstrated a link between filamentation and virulence; however, relatively little is known regarding the role of the filament-to-yeast transition during the pathogenesis of invasive candidiasis. We previously identified the C. albicans pescadillo homolog ( PES1 ) as essential during yeast growth and growth of lateral yeast on hyphae but not during hyphal growth. Furthermore, we demonstrated that PES1 is required for virulence in vivo in a Galleria mellonella larva model of candidiasis. Here, we have used a regulatable tetO-PES1 / pes1 strain to …
Use of a Genetically Engineered Strain To Evaluate the Pathogenic Potential of Yeast Cell and Filamentous Forms duringCandida albicansSystemic Infection in Immunodeficient Mice
ABSTRACTThe pathogenesis ofCandida albicanssystemic infection is complex and results from the balance between its intrinsic virulence attributes and the host immune responses. Morphogenetic transitions between yeast cell and filamentous forms are considered one of the main virulence attributes inC. albicans. We have examined the pathogenesis of a genetically engineeredC. albicansstrain in which morphogenetic conversions can be externally manipulated in immunodeficient mice; these included B-cell deficient, nude (T cell deficient), SCID (lacking both functional T and B cells), and DBA/2N (C5 deficient with impaired neutrophil activity) mice. We also tested mice severely immunosuppressed by c…
Efficacy of a genetically engineered Candida albicans tet-NRG1 strain as an experimental live attenuated vaccine against hematogenously disseminated candidiasis.
ABSTRACT We report on the efficacy of the genetically engineered Candida albicans tet-NRG1 strain as an experimental live, attenuated vaccine against disseminated candidiasis in both immunocompetent and immunodeficient mice mostly dependent on T-cell immunity. This experimental vaccination model may represent an important tool to unravel the mechanisms of protective immunity during candidiasis.