All ETDs from UAB

Advisory Committee Chair

Louis B Justement

Advisory Committee Members

Peter D Burrows

Robert H Carter

Christopheer A Klu

Michael J Ruppert

Andries J Steyn

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is still a major threat to the human population. Roughly one third of the world population is asymptomatically infected and two million people die each year of TB. Effective treatments are available as a multi-drug regimen, but there is an ever increasing problem with the rise of multi-drug resistant strains that newer drug targets and a better understanding of how M. tuberculosis affects the host need to be elucidated. The primary target of M. tuberculosis in the human host is the macrophage where M. tuberculosis secretes virulence factors that inhibit various signal transduction pathways in order for intracellular survival. One such virulence factor is MPtpB, a protein tyrosine phosphatase. Tyrosine phosphorylation is an important factor in regulating various host cell processes. To better understand how MPtpB affects the host, we wanted to determine the targets of MPtpB in the macrophage. We also looked at what other virulence factors of M. tuberculosis MPtpB might interact with to help increase its virulence upon the macrophage. MPtpB was shown to interact with enhanced intracellular survival (Eis) protein. To delineate the function of Eis, a BLAST search was performed and revealed Eis to have a putative acetyltransferase site. We determine that Eis is capable of acetylating free histones but not histones found in a nucleosomal complex. Eis was also shown to inhibit the phosphatase activity of MPtpB in vitro using pNPP as a substrate.



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