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The Phosphodiesterase, Rv0805, Is An Unheralded Component Of Tb Complex Mycobacterial Physiology In And Beyond Camp Homeostasis, James R. Mcdowell
The Phosphodiesterase, Rv0805, Is An Unheralded Component Of Tb Complex Mycobacterial Physiology In And Beyond Camp Homeostasis, James R. Mcdowell
Legacy Theses & Dissertations (2009 - 2024)
Phosphodiesterases (PDEs) are integral components of 3’,5’-cyclic adenosine monophosphate (cAMP) signaling pathways by degrading cAMP to modulate the concentration, duration, and localization of the cAMP signal which maintains the specificity of cAMP pathways. The human pathogen, Mycobacterium tuberculosis (Mtb) has a unique cAMP network architecture with at least 15 adenylyl cyclases (ACs) that generate cAMP, but only one characterized PDE, Rv0805, which is found exclusively in pathogenic mycobacteria. Rv0805 can influence Mtb cAMP levels but the absence of Rv0805 orthologs in non-pathogenic mycobacteria and apparent separation of Rv0805 from cAMP directed roles led to numerous questions surrounding PDE function in …
Cyclic Adenosine Monophosphate Signaling In Mycobacterium Tuberculosis : New Insights Into A Universal Second Messenger, Richard Mcpherson Johnson
Cyclic Adenosine Monophosphate Signaling In Mycobacterium Tuberculosis : New Insights Into A Universal Second Messenger, Richard Mcpherson Johnson
Legacy Theses & Dissertations (2009 - 2024)
Despite being the focus of intense research for many years Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains the deadliest bacterial pathogen plaguing mankind today. Humans are the sole host and reservoir for Mtb, and Mtb has coevolved closely with its human host for thousands of years. Mtb currently infects over two billion people worldwide and over 1.5 million people die from TB each year, arguably making Mtb the most successful bacterial pathogen on the planet.
Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty
Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty
Legacy Theses & Dissertations (2009 - 2024)
As an innate defense mechanism, macrophages produce reactive species that weaken pathogens and serve as secondary messengers to modify signaling responses involved in immune function. The gram-negative bacterium F. tularensis utilizes its antioxidant armature to limit the host immune response but the mechanism behind this suppression has not been defined. Here we establish that F. tularensis limits Ca2+ entry thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild-type (LVS) or catalase deficient F. tularensis (∆katG) show distinct profiles in their H2O2 scavenging capacity, 1 pM/sec and 0.015 pM/sec, respectively. Murine alveolar macrophages infected with ∆katG display distinct …