A VirB4 ATPase of the mobile accessory genome orchestrates core genome-encoded features of physiology, metabolism, and virulence of TBCF10839.

TBCF10839 is a highly virulent strain that can persist and replicate in human neutrophils. Screening of a signature-tagged mutagenesis (STM) TBCF10839 transposon library in phagocytosis tests identified a mutant that carried the transposon in the VirB4 homolog 5PG21 of an integrative and conjugative element (ICE)-associated type IV secretion system of the pKLC102 subtype. 5P21 TBCF10839 insertion mutants were deficient in metabolic versatility, secretion, quorum sensing, and virulence.

SMAR1 inhibits Wnt/β-catenin signaling and prevents colorectal cancer progression.

Reduced expression of Scaffold/Matrix Attachment Region Binding Protein 1 (SMAR1) is associated with various cancers resulting in poor prognosis of the diseases. However, the precise underlying mechanism elucidating the loss of SMAR1 requires ongoing study. Here, we show that SMAR1 is highly downregulated during aberrant Wnt3a signaling due to proteasomal degradation and predicted poor prognosis of colorectal cancer.

Intraclonal diversity of the Pseudomonas aeruginosa cystic fibrosis airway isolates TBCF10839 and TBCF121838: distinct signatures of transcriptome, proteome, metabolome, adherence and pathogenicity despite an almost identical genome sequence.

Microevolution of closely related Pseudomonas aeruginosa was compared in the clone TB strains TBCF10839 and TBCF121838 which had been isolated from two unrelated individuals with cystic fibrosis who had acquired clone TB during a local outbreak. Compared with the strain PAO1 reference sequence the two clone TB genomes shared 23 155 nucleotide exchanges, 32 out-of-frame indels in the coding region and another repertoire of replacement and genomic islands such as PAGI-1, PAGI-2, PAGI-5, LESGI-1 and LES-prophage 4. Only TBCF121838 carried a genomic island known from Ralstonia pickettii.

Glioblastoma multiforme: novel therapeutic approaches.

The current therapy for glioblastoma multiforme involves total surgical resection followed by combination of radiation therapy and temozolomide. Unfortunately, the efficacy for such current therapy is limited, and newer approaches are sorely needed to treat this deadly disease. We have recently described the isolation of bacterial proteins and peptides with anticancer activity.

Multiple roles of Pseudomonas aeruginosa TBCF10839 PilY1 in motility, transport and infection.

Polymorphonuclear neutrophils are the most important mammalian host defence cells against infections with Pseudomonas aeruginosa. Screening of a signature tagged mutagenesis library of the non-piliated P. aeruginosa strain TBCF10839 uncovered that transposon inactivation of its pilY1 gene rendered the bacterium more resistant against killing by neutrophils than the wild type and any other of the more than 3000 tested mutants.

Functional genomics of Pseudomonas aeruginosa to identify habitat-specific determinants of pathogenicity.

Half of all genes in the Pseudomonas aeruginosa genome have either no homology to any previously reported sequence or are homologues of previously reported genes of unknown function. The signature-tagged mutagenesis (STM) screening method allows to explore the role of these hypothetical and unknown proteins for the colonization and persistence of P. aeruginosa in eukaryotic hosts.

Identification and characterization of a novel bacterial virulence factor that shares homology with mammalian Toll/interleukin-1 receptor family proteins.

Many important bacterial virulence factors act as mimics of mammalian proteins to subvert normal host cell processes. To identify bacterial protein mimics of components of the innate immune signaling pathway, we searched the bacterial genome database for proteins with homology to the Toll/interleukin-1 receptor (TIR) domain of the mammalian Toll-like receptors (TLRs) and their adaptor proteins. A previously uncharacterized gene, which we have named tlpA (for TIR-like protein A), was identified in the Salmonella enterica serovar Enteritidis genome that is predicted to encode a protein resembling mammalian TIR domains, We show that overexpression of TlpA in mammalian cells suppresses the ability of mammalian TIR-containing proteins TLR4, IL-1 receptor, and MyD88 to induce the transactivation and DNA-binding activities of NF-kappaB, a downstream target of the TIR signaling pathway.

A cystic fibrosis epidemic strain of Pseudomonas aeruginosa displays enhanced virulence and antimicrobial resistance.

The Liverpool epidemic strain (LES) of Pseudomonas aeruginosa is a transmissible aggressive pathogen of cystic fibrosis (CF) patients. We compared transcriptome profiles of two LES isolates with each other and with a laboratory and genetic reference strain (PAO1) after growth to late exponential phase and following exposure to oxidative stress. Both LES isolates exhibited enhanced antimicrobial resistances linked to specific mutations in efflux pump genes.

Genome-wide transcriptional profiling of the steady-state response of Pseudomonas aeruginosa to hydrogen peroxide.

The steady-state response of Pseudomonas aeruginosa to the oxidative-stress-generating agent hydrogen peroxide was analyzed by PAO1 transcriptome profiling. In total, 694, 411, and 237 genes were upregulated and 668, 576, and 468 genes were downregulated in P. aeruginosa strains TB, 892, and PAO1, respectively.

GeneChip expression analysis of the VqsR regulon of Pseudomonas aeruginosa TB.

Two interlinked quorum sensing circuits, las and rhl, which control pathogenesis of Pseudomonas aeruginosa are further modulated by numerous regulators, including VqsR (virulence and quorum sensing regulator). High-density oligonucleotide microarrays were used to compare the global expression profile of a wild-type and VqsR mutant in ABC minimal medium. The expression of a large group of metabolic genes, ECF sigma factors as well as of many quorum-sensing genes previously not assigned to VqsR-regulon was found to be affected by the disruption of vqsR.

Evidence for polyadenylated mRNA in Pseudomonas aeruginosa.

In this paper, we report the synthesis of Pseudomonas aeruginosa cDNA in the presence of oligo(dT) primers. Hybridization of oligonucleotide DNA microarrays indicates that under the experimental conditions used, at least 43.7% of the expressed genes from P.

Global regulation of quorum sensing and virulence by VqsR in Pseudomonas aeruginosa.

Pathogenesis of Pseudomonas aeruginosa is controlled to a major extent by the two quorum-sensing systems las and rhl. The previously uncharacterized gene PA2591 was identified as a major virulence regulator, vqsR, in the quorum-sensing hierarchy. vqsR is a member of the LuxR family and possesses a las box in its upstream region.