Cellular Metabolic Network Analysis: Discovering Important Reactions in Treponema pallidum

TL;DR

This paper identifies key metabolic reactions in Treponema pallidum, the syphilis-causing bacterium, to help develop better treatments and vaccines.

Contribution

The study uses Flux Balance Analysis and minimal cut sets to identify critical metabolic reactions in T. pallidum.

Findings

Two types of reactions in nucleic acid metabolism are essential for T. pallidum.

Hubs and isolated reactions in purine and pyrimidine metabolisms are important for the pathogen.

The approach helps identify potential drug targets specific to T. pallidum.

Abstract

T. pallidum, the syphilis-causing pathogen, performs very differently in metabolism compared with other bacterial pathogens. The desire for safe and effective vaccine of syphilis requests identification of important steps in T. pallidum's metabolism. Here, we apply Flux Balance Analysis to represent the reactions quantitatively. Thus, it is possible to cluster all reactions in T. pallidum. By calculating minimal cut sets and analyzing topological structure for the metabolic network of T. pallidum, critical reactions are identified. As a comparison, we also apply the analytical approaches to the metabolic network of H. pylori to find coregulated drug targets and unique drug targets for different microorganisms. Based on the clustering results, all reactions are further classified into various roles. Therefore, the general picture of their metabolic network is obtained and two types of reactions, both of which are involved in nucleic acid metabolism, are found to be essential for T. pallidum. It is also discovered that both hubs of reactions and the isolated reactions in purine and pyrimidine metabolisms play important roles in T. pallidum. These reactions could be potential drug targets for treating syphilis.

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