Laboratory Researct @ HMC
R&T Center
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R&T Center2

Lorenzo Giacani, PhD
Acting Instructor, Department of Medicine

In untreated syphilis, Treponema pallidum is able to disseminate to and replicate in virtually every organ, evade the host immune response, and latently persist in the infected individual for a lifetime. Late manifestations, following disease reactivation, include insanity, paralysis or even death. The importance of the molecular mechanisms that maintain the integrity and functionality of T. pallidum envelope (outer, inner membranes and periplasmic space) in response to growth- and host- induced stresses has never been addressed as a key element to immune evasion, adaptation, and persistence in syphilis. This application proposes to examine molecular mechanisms that likely affect persistence of T. pallidum. We hypothesize that, similarly to other Gram-negative pathogens, the transcription factor σE is a key player in maintaining T. pallidum envelope homeostasis. σE is highly transcribed during early experimental syphilis, and its expression significantly increases when immune clearance of the pathogen begins. Furthermore, σE binding motifs can be identified in silico upstream of a variety of genes that, in other pathogens, were experimentally shown to be involved in envelope stress response. To test our hypothesis, we will identify the T. pallidum σE regulon (all σE-controlled genes in the T. pallidum chromosome) and compare it to other pathogens’ σE regulons. As well, we will investigate how expression of σE-dependent genes varies during experimental infection in treponemes harvested before and after development of the host’s adaptive immune response. Based on the increment of the expression levels of these genes, we will predict what T. pallidum genes play a key role in maintaining envelope homeostasis. These studies will provide new insight into the mechanisms that contribute to T. pallidum’s ability to evade the host immune response, persist, as well as adapt to so many different host environments.


 

Location: RT 621 (lab)/RT 603 (office)
Phone: (206) 897-5402, (206) 897-5360
Email:
giacal@u.washington.edu, loreznogiacani@gmail.com

 

 

 

 

 

 

 

 

 

 

Copyright University of Washington - Last Updated 11/22/2009 by Miko Robertson