Francisella tularensis metabolism and its relation to virulence

Abstract

Francisella tularensis is a Gram-negative bacterium capable of causing the zoonotic disease tularaemia in a large number of mammalian species and in arthropods. F. tularensis is a facultative intracellular bacterium that infects and replicates in vivo mainly inside macrophages. During its systemic dissemination, F. tularensis must cope with very different life conditions (such as survival in different target organs or tissues and/or survival in the blood stream…) and may thus encounter a broad variety of carbon substrates, nitrogen, phosphor, and sulfur sources, as well as very low concentrations of essential ions. The development of recent genome-wide genetic screens have led to the identification of hundreds of genes participating to variable extents to Francisella virulence. Remarkably, an important proportion of the genes identified are related to metabolic and nutritional functions. However, the relationship between nutrition and the in vivo life cycle of F. tularensis is yet poorly understood. In this review, we will address the importance of metabolism and nutrition for F. tularensis pathogenesis, focusing specifically on amino acid and carbohydrate requirements.

Keywords: Francisella tularensis; metabolism; pathogenesis.

Figure 1

The shikimate pathway. Genes that have been identified in genetic screens (in vivo or in vitro) are underlined. Genes that have not been hit in any screen are in blue. TrpD*, the gene is absent in the Schu S4 and LVS strains but present in the subsp. novicida (FTA_2078). TyrA*, the gene is absent in the Schu S4 strain but present in both LVS (FTL_048) and subsp. novicida (FTN_0055).

Figure 2

The purine biosynthetic pathway. Genes that have been identified in genetic screens (in vivo or in vitro) are underlined. Genes that have not been hit in any screen are in blue.

Figure 3

The pyrimydine biosynthetic pathway. Genes that have been identified in genetic screens (in vivo or in vitro) are underlined. Genes that have not been hit in any screen are in blue.

Figure 4

The glycolytic and gluconeogenic pathways. GlpX is the only enzyme not promoting a reversible reaction. Genes that have been identified in genetic screens (in vivo or in vitro) are underlined. Genes that have not been hit in any screen are in blue. Genes predicted to be essential (according to Gallagher et al., 2007) are in red. The black dotted arrows indicate the connection between the glycolytic/gluconeogenic pathways and the pentose phosphate and fructose pathways. In each pathway, the gene name is indicated to the left of each reaction and the corresponding FTT number, to the right.