TylA has an essential virulence role in mycobacterium tuberculosis pathogenesis.
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Date
2015
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Abstract
Mycobacterium tuberculosis (M.tb), the causative agent of the disease tuberculosis, is an ancient pathogen and a major cause of death worldwide. Although various virulence factors of M.tb have been identified, its pathogenesis remains incompletely understood. TlyA is a virulence factor that is evolutionarily conserved in many gram-positive bacteria, but its function in the pathogenesis of infection with M.tb has not been elucidated. Here, we report that TlyA cause translocation of M.tb from phagolysosome into the cytosol in murine macrophages, which is the key to mycobacterial pathogenesis. In this study we also showed that TlyA mutant M.tb strain induces increased IL-12 and reduced IL-1β and IL-10 cytokine responses, which is in contrast to the immune responses induced by wild type M.tb. Mice infected with TlyA deficient mutant M.tb organisms exhibited increased host protective immune responses, reduced bacillary load, and increased survival compared with animals infected with wild type M.tb. Therefore it is likely that M.tb employs TlyA as a host evasion factor, thereby contributing to its virulence.
Description
Doctor of Philosophy in Medical Microbiology. University of KwaZulu-Natal, Medical School 2015.
Keywords
Mycobacterium tuberculosis., Pathogenic viruses., Tuberculosis -- Immunology., Viruses -- Morphology., Theses -- Medical microbiology.