The complete genome sequence of Francisella tularensis, the causative agent of tularemia

Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them.     

Stepwise enzymatic dephosphorylation of inositol 1,4,5-trisphosphate to inositol in liver

Many receptors for hormones, neurotransmitters and other signals cause hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and effect a rise in cytosolic Ca2+ concentration. The inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) liberated during PtdIns(4,5)P2 breakdown seems to serve as a second messenger that activates the release of Ca2+ from a nonmitochondrial intracellular compartment. As expected if it is an important intracellular messenger, Ins(1,4,5)P3 is relatively rapidly degraded, both within stimulated cells and when added to homogenates of blowfly salivary gland or to permeabilized, but not intact, hepatocytes. Here we report that the dephosphorylation reactions responsible for the conversion of Ins(1,4,5)P3 to free inositol in rat liver are catalysed by two or more enzymes, and that these reactions are distributed between the plasma membrane and cytosol. The Ins(1,4,5)P3 5-phosphatase and inositol 1-phosphate (Ins(1)P) phosphatase of liver appear similar to enzymes described previously in erythrocytes and brain.