Temporal transcriptomic analysis of the Listeria monocytogenes EGD-e σB regulon

<p>Abstract</p> <p>Background</p> <p>The opportunistic food-borne gram-positive pathogen <it>Listeria monocytogenes </it>can exist as a free-living microorganism in the environment and grow in the cytoplasm of vertebrate and invertebrate cells following infection. The general stress response, controlled by the alternative sigma factor, σ^B, has an important role for bacterial survival both in the environment and during infection. We used quantitative real-time PCR analysis and immuno-blot analysis to examine σ^Bexpression during growth of <it>L. monocytogenes </it>EGD-e. Whole genome-based transcriptional profiling was used to identify σ^B-dependent genes at different growth phases.</p> <p>Results</p> <p>We detected 105 σ^B-positively regulated genes and 111 genes which appeared to be under negative control of σ^Band validated 36 σ^B-positively regulated genes <it>in vivo </it>using a reporter gene fusion system.</p> <p>Conclusion</p> <p>Genes comprising the σ^Bregulon encode solute transporters, novel cell-wall proteins, universal stress proteins, transcriptional regulators and include those involved in osmoregulation, carbon metabolism, ribosome- and envelope-function, as well as virulence and niche-specific survival genes such as those involved in bile resistance and exclusion. Ten of the σ^B-positively regulated genes of <it>L. monocytogenes </it>are absent in <it>L. innocua</it>. A total of 75 σ^B-positively regulated listerial genes had homologs in <it>B. subtilis</it>, but only 33 have been previously described as being σ^B-regulated in <it>B. subtilis </it>even though both species share a highly conserved σ^B-dependent consensus sequence. A low overlap of genes may reflects adaptation of these bacteria to their respective environmental conditions.</p

Complete Genome Sequence of Listeria seeligeri, a Nonpathogenic Member of the Genus Listeria▿

We report the complete and annotated genome sequence of the nonpathogenic Listeria seeligeri SLCC3954 serovar 1/2b type strain harboring the smallest completely sequenced genome of the genus Listeria

Functional COG categories of σ-differential regulated genes of EGD-e obtained from temporal transcriptome profiling experiments

<p><b>Copyright information:</b></p><p>Taken from "Temporal transcriptomic analysis of the EGD-e σregulon"</p><p>http://www.biomedcentral.com/1471-2180/8/20</p><p>BMC Microbiology 2008;8():20-20.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2248587.</p><p></p> Functional categories were determined using COG for provided by NCBI [62]. The figure was drawn using the Augur software [71]

(A) Copy number of the gene in EGD-e grown in BHI medium for 3 h, 4 h, 8 h and 16 h

<p><b>Copyright information:</b></p><p>Taken from "Temporal transcriptomic analysis of the EGD-e σregulon"</p><p>http://www.biomedcentral.com/1471-2180/8/20</p><p>BMC Microbiology 2008;8():20-20.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2248587.</p><p></p> Data shown here is representative of three independent biological replicates. (B) Immuno-blot analysis quantifying σfrom EGD-e at different growth phases. Proteins were isolated from cultures of EGD-e grown for 3 h (lane 1), 4 h (lane 2), 8 h (lane 3) and 16 h (lane 4) in BHI at 37°C and σwas detected using rabbit polyclonal anti-serum produced against COL σ. The Δdeletion mutant (lane 5) was used as negative control and COL (lane 6) was used as positive control for specific binding of the antibody. Molecular masses (in kilodaltons) of prestained SDS-PAGE standard marker (Bio-Rad) are indicated on the left and σis marked on the right

Targeting Wnt-ß-Catenin-FOSL Signaling Ameliorates Right Ventricular Remodeling

BACKGROUND: The ability of the right ventricle (RV) to adapt to an increased pressure afterload determines survival in patients with pulmonary arterial hypertension. At present, there are no specific treatments available to prevent RV failure, except for heart/lung transplantation. The wingless/int-1 (Wnt) signaling pathway plays an important role in the development of the RV and may also be implicated in adult cardiac remodeling. METHODS: Molecular, biochemical, and pharmacological approaches were used both in vitro and in vivo to investigate the role of Wnt signaling in RV remodeling. RESULTS: Wnt/β-catenin signaling molecules are upregulated in RV of patients with pulmonary arterial hypertension and animal models of RV overload (pulmonary artery banding-induced and monocrotaline rat models). Activation of Wnt/β-catenin signaling leads to RV remodeling via transcriptional activation of FOSL1 and FOSL2 (FOS proto-oncogene [FOS] like 1/2, AP-1 [activator protein 1] transcription factor subunit). Immunohistochemical analysis of pulmonary artery banding -exposed BAT-Gal (β-catenin-activated transgene driving expression of nuclear β-galactosidase) reporter mice RVs exhibited an increase in β-catenin expression compared with their respective controls. Genetic inhibition of β-catenin, FOSL1/2, or WNT3A stimulation of RV fibroblasts significantly reduced collagen synthesis and other remodeling genes. Importantly, pharmacological inhibition of Wnt signaling using inhibitor of PORCN (porcupine O-acyltransferase), LGKK-974 attenuated fibrosis and cardiac hypertrophy leading to improvement in RV function in both, pulmonary artery banding - and monocrotaline-induced RV overload. CONCLUSIONS: Wnt- β-Catenin-FOSL signaling is centrally involved in the hypertrophic RV response to increased afterload, offering novel targets for therapeutic interference with RV failure in pulmonary hypertension