Global transcriptional response to spermine, a component of the intra-macrophage environment, reveals regulation of Francisella gene expression through insertion sequence elementsDocUID: 2009-019 Full Text: PDF
Author: Paul E. Carlson Jr., Joseph Horzempa, Dawn M. O'Dee, Cory M. Robinson, Panayiotis Neophytou, Alexandros Labrinidis, Gerard J. Nau
Abstract: Tularemia is caused by the Category A biodefense agent, Francisella tularensis. This bacterium is associated with diverse environments and a plethora of arthropod and mammalian hosts. How F. tularensis adapts to these different conditions, particularly the eukaryotic intracellular environment in which it replicates, is poorly understood. Here we demonstrate that the polyamines spermine and spermidine are environmental signals that alter bacterial stimulation of host cells. Genome-wide analysis showed that F. tularensis LVS undergoes considerable changes in gene expression in response to spermine. Unexpectedly, analysis of gene expression showed that multiple members of two classes of Francisella insertion sequence (IS) elements, isftu1 and isftu2, and the genes adjacent to these elements were induced by spermine. Spermine was sufficient to activate transcription of these IS elements and of nearby genes in broth culture and in macrophages. Importantly, the virulent strain of F. tularensis, Schu S4, exhibited similar phenotypes of cytokine induction and gene regulation in response to spermine. Distinct gene expression changes between Schu S4 and LVS at one orthologous locus, however, correlated with differences in IS element location. Our results indicate that spermine and spermidine are novel triggers to alert F. tularensis of its eukaryotic host environment. The results here also identify an unexpected mechanism of gene regulation controlled by a spermine-responsive promoter contained within IS elements. Different arrangements of these mobile genetic elements among Francisella strains could contribute to virulence by conveying new expression patterns on genes from different strains.
Published In: Journal of Bacteriology
Year Published: 2009
Project: CMPI Subject Area: Others
Publication Type: Journal Paper
Sponsor: NIH-NIAID NO1-AI50018