To establish a successful infection, Bacillus anthracis, the etiological agent for anthrax, has to compete with its host for a variety of nutrients, including iron. Iron is generally sequestered by iron transport proteins, iron storage proteins, or by cofactors utilizing iron.  To capture iron, B. anthracis secretes high affinity metal chelators known as siderophores. In this work, a genome-scale metabolic reconstruction incorporating siderphore effects was created.  The model was then used to evaluate the overall impact of iron availability on B. anthracis metabolism.  Genome-scale metabolic models allow for the compact and integrated analysis of complex metabolic networks and their associated, often non-intuitive, behavior. The model was validated using experimental growth data for B. anthracis under iron-poor/rich conditions. During the course of the experiments for both iron conditions, two metabolic phases were observed. Phase I was characterized by lactate production, while in Phase II lactate was consumed. Using the B. anthracis model, the metabolic response to iron availability under both Phase I and Phase II were examined. During Phase I, the main metabolic pathways of B. anthracis exhibited similar behavior under both iron-poor and iron-rich conditions. As a result, the levels of iron in the iron-poor culture were sufficient to support almost normal growth of the bacteria. In Phase II, on the contrary, many changes were observed in the main metabolic pathways between the iron-rich and iron-poor conditions. The more significant ones included downregulation of the reactions of the TCA cycle and a reduction in the uptake of certain amino acids under iron-poor conditions.

Genome-scale metabolic analysis of the iron acquisition system in of <i>Bacillus anthracis </i>

247th National Meeting (2014)

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Genome-scale metabolic analysis of the iron acquisition system in of Bacillus anthracis