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Understanding virulence mechanisms in M. tuberculosis infection via a circuit-based simulation framework.

Conference ·
OSTI ID:947821

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), is a growing international health crisis. Mtb is able to persist in host tissues in a non-replicating persistent (NRP) or latent state. This presents a challenge in the treatment of TB. Latent TB can re-activate in 10% of individuals with normal immune systems, higher for those with compromised immune systems. A quantitative understanding of latency-associated virulence mechanisms may help researchers develop more effective methods to battle the spread and reduce TB associated fatalities. Leveraging BioXyce's ability to simulate whole-cell and multi-cellular systems we are developing a circuit-based framework to investigate the impact of pathogenicity-associated pathways on the latency/reactivation phase of tuberculosis infection. We discuss efforts to simulate metabolic pathways that potentially impact the ability of Mtb to persist within host immune cells. We demonstrate how simulation studies can provide insight regarding the efficacy of potential anti-TB agents on biological networks critical to Mtb pathogenicity using a systems chemical biology approach

Research Organization:
Sandia National Laboratories (SNL), Albuquerque, NM, and Livermore, CA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC04-94AL85000
OSTI ID:
947821
Report Number(s):
SAND2008-5493C; TRN: US200905%%187
Resource Relation:
Conference: Proposed for presentation at the 30th Annual International Conference of the IEEE EMB held August 20-24, 2008 in Vancouver, BC.
Country of Publication:
United States
Language:
English