Stat3 activation has been associated with cytokine-induced proliferation, anti-apoptosis, and transformation. Constitutively activated found in many human tumors as well v-abl- v-src-transformed cell lines. Because of these correlations, we examined directly the relationship to cellular transformation that wild-type enhances transforming potential v-src while three dominant negative mutants inhibit v-srctransformation. or mutant proteins did not affect v-ras We conclude a necessary role

Although pneumonic plague is the deadliest manifestation of disease caused by bacterium Yersinia pestis, there surprisingly little information on cellular and molecular mechanisms responsible for Y. pestis-triggered pathology in lung. Therefore, to understand progression this unique disease, we characterized an intranasal mouse model primary plague. Mice succumbed a purulent multifocal severe exudative bronchopneumonia that closely resembles observed humans. Analyses revealed strikingly...

Primary pneumonic plague is transmitted easily, progresses rapidly, and causes high mortality, but the mechanisms by which Yersinia pestis overwhelms lungs are largely unknown. We show that plasminogen activator Pla essential for Y. to cause primary less important dissemination during than bubonic plague. Experiments manipulating its temporal expression showed allows replicate rapidly in airways, causing a lethal fulminant pneumonia; if unexpressed, inflammation aborted, lung repair...

The pathogenic species of Yersinia contain the transcriptional regulator RovA. In pseudotuberculosis and enterocolitica , RovA regulates expression invasion factor invasin ( inv ), which mediates translocation across intestinal epithelium. A Y . rov mutant has a significant decrease in virulence by LD 50 analysis an altered rate dissemination compared with either wild type or mutant, suggesting that multiple factors. Here, we show involvement pestis naturally lacks functional gene. Δrov is...

Summary Escherichia coli O157:H7 causes diarrhoea, haemorrhagic colitis, and the haemolytic uraemic syndrome. We have identified a protein of previously unknown function encoded on pO157 virulence plasmid E. O157:H7, which is first described protease that specifically cleaves C1 esterase inhibitor (C1‐INH), member serine family. The protein, named StcE for s ecreted pro t ease C 1 from E HEC (formerly Tagn), C1‐INH to produce (unique) ≈ 60–65 kDa fragments. does not digest other inhibitors,...

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a diarrheal pathogen that causes attaching and effacing (A/E) lesions on intestinal epithelial cells. Strains of the O157 serogroup carry large virulence plasmid pO157, which encodes etp type II secretion system secretes genetically linked zinc metalloprotease StcE. The Ler regulator controls expression many genes involved in A/E lesion formation, as well StcE, suggesting StcE may be important at similar time during colonization....

A major class of bacterial small, noncoding RNAs (sRNAs) acts by base-pairing with mRNAs to alter the translation from and/or stability transcript. Our laboratory has shown that Hfq, chaperone mediates interaction many sRNAs their targets, is required for virulence enteropathogen Yersinia pseudotuberculosis . This finding suggests play a critical role in regulation this pathogen, but these are not known. Using deep sequencing approach, we identified global set expressed vitro Y. Sequencing...

Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. recently evolved from gastrointestinal pathogen pseudotuberculosis; however, it is not known at what point gained ability to induce a fulminant pneumonia. Here we show that acquisition of single gene encoding protease Pla was sufficient for most ancestral, deeply rooted strains cause plague, indicating primed infect lungs very early stage in its evolution. As further evolved, modern acquired amino-acid modification...

ABSTRACT Bacterial small, noncoding RNAs (sRNAs) participate in the posttranscriptional regulation of gene expression, often by affecting protein translation, transcript stability, and/or activity. For proper function, many sRNAs rely on chaperone Hfq, which mediates interaction sRNA with its target mRNA. Recent studies have demonstrated that Hfq contributes to pathogenesis a number bacterial species, suggesting play an essential role virulence. The enteric pathogen Yersinia...

Many Gram-negative bacteria produce outer membrane vesicles (OMVs) during cell growth and division, some bacterial pathogens deliver virulence factors to the host via release of OMVs infection. Here we show that Yersinia pestis, causative agent disease plague, produces releases native under physiological conditions. These OMVs, approximately 100 nm in diameter, contain multiple virulence-associated proteins including adhesin Ail, F1 fimbrial antigen, protease Pla. We found released by Y....

Yersinia pestis, the cause of disease plague, forms biofilms to enhance flea-to-mammal transmission. Biofilm formation is dependent on exopolysaccharide synthesis and controlled by intracellular levels second messenger molecule cyclic diguanylate (c-di-GMP), but mechanisms which Y. pestis regulates c-di-GMP turnover are not fully understood. Here we show that small RNA chaperone Hfq contributes regulation biofilm modulating abundance both phosphodiesterase HmsP cyclase HmsT. To do so,...

Small noncoding RNA (sRNA) molecules are integral components of the regulatory machinery for many bacterial species and known to posttranscriptionally regulate metabolic stress-response pathways, quorum sensing, virulence factors, more. The Yop-Ysc type III secretion system (T3SS) is a critical component pathogenic Yersinia species, regulation this tightly controlled at each step from transcription translocation effectors into host cells. contribution sRNAs T3SS in has been largely...

The complement system is an essential component of host defense against pathogens. Previous research in our laboratory identified StcE, a metalloprotease secreted by Escherichia coli O157:H7 that cleaves the serpin C1 esterase inhibitor (C1-INH), major regulator classical cascade. Analyses StcE-treated C1-INH activity revealed surprisingly, StcE enhanced ability to inhibit complement-mediated lysis sheep erythrocytes. directly interacts with both cells and C1-INH, thereby binding cell...

The cyclic AMP receptor protein (Crp) is a transcriptional regulator that controls the expression of numerous bacterial genes, usually in response to environmental conditions and particularly by sensing availability carbon. In plague pathogen Yersinia pestis, Crp regulates multiple virulence factors, including components type III secretion system plasminogen activator protease Pla. regulation itself, however, distinctly different from found well-studied Escherichia coli system. Here, we show...

Klebsiella pneumoniae has a reputation for causing wide range of infectious conditions, with numerous highly virulent and antibiotic-resistant strains. Metabolic models have the potential to provide insights into growth behavior, nutrient requirements, essential genes, candidate drug targets in these Here we develop metabolic model KPPR1, strain K. pneumoniae. We apply combination Biolog phenotype data fitness validate refine our KPPR1 model. The final displays predictive accuracy 75%...

Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, causative agent of plague, expresses plasminogen activator protease Pla, which has been shown in vitro target and cleave multiple proteins within fibrinolytic pathway, including plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP vivo; role respiratory Y. pestis known either. Here, we show that does appreciably a Pla-dependent manner lungs...

Essentials Effect of plasminogen activator inhibitor (PAI)-1 on plague and its Y. pestis cleavage is unknown. An intranasal mouse model infection was used to determine the role PAI-1 in pneumonic plague. cleaved inactivated by Pla protease lung airspace. impacts both bacterial outgrowth immune response respiratory infection. Click hear Dr Bock discuss pathogen activators plasminogen.Background The hemostatic regulator inhibitor-1 (PAI-1) inactivates endogenous aids Yersinia pestis, causative...

Escherichia coli O157:H7 is a source of foodborne illness, causing diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome. E. secretes, via the etp type II secretion system, metalloprotease, StcE, that specifically cleaves serpin C1 esterase inhibitor. We determined by hybridization techniques prevalence stcE etpD gene, among diarrheagenic strains. are ubiquitous serotype found in some enteropathogenic O55:H7 strains but absent from other coli. was acquired on large plasmid early...

Yersinia pestis, the causative agent of plague, uses a type III secretion system (T3SS) to inject cytotoxic Yop proteins directly into cytosol mammalian host cells. The T3SS can also be activated in vitro at 37°C absence calcium. chromosomal gene rfaL (waaL) was recently identified as virulence factor required for proper function T3SS. RfaL functions ligase that adds terminal N-acetylglucosamine lipooligosaccharide core Y. pestis. We previously showed deletion prevents Yops vitro. Here we...