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At least 1,693 records · Page 94Linked to original sources
PubMed2006

Detection of a phage genome carrying a zonula occludens like toxin gene (zot) in clinical isolates of Stenotrophomonas maltophilia.

During a study of the genetic diversity of Stenotrophomonas strains, we found an autonomous replicating DNA molecule in chromosomal DNA preparations of the clinical Stenotrophomonas maltophilia strain c5. The entire sequence of 6,907 bp of the isolated DNA molecule was determined, which was called phiSMA9. Seven ORFs, which code for proteins with considerable similarity to proteins in databases, were identified in the DNA sequence. The largest ORF shows high sequence similarities to the pI protein of the filamentous phage phiLf, which was later shown to be identical to toxin Zot of Vibrio cholerae. Beside the Zot-like protein, six other proteins with similarities to known phage proteins such as a phage replication protein RstA and phage absorption or coat protein are encoded on phiSMA9, which indicate that this circular DNA molecule represents the replicative form of a linear phage genome. A PCR-based screening showed that only five from the totally investigated 47 Stenotrophomonas strains of clinical and environmental origin harbor these genes. Altogether, we describe the first genome of a phage for the nosocomial pathogen Stenotrophomonas, which contains a Zot toxin like gene and might be regarded as the first Stenotrophomonas virulence factor.

Amino Acid Sequence↗
PubMed2000

Measurement of bacterial gene expression in vivo.

The complexities of bacterial gene expression during mammalian infection cannot be addressed by in vitro experiments. We know that the infected host represents a complex and dynamic environment, which is modified during the infection process, presenting a variety of stimuli to which the pathogen must respond if it is to be successful. This response involves hundreds of ivi (in vivo-induced) genes which have recently been identified in animal and cell culture models using a variety of technologies including in vivo expression technology, differential fluorescence induction, subtractive hybridization and differential display. Proteomic analysis is beginning to be used to identify IVI proteins, and has benefited from the availability of genome sequences for increasing numbers of bacterial pathogens. The patterns of bacterial gene expression during infection remain to be investigated. Are ivi genes expressed in an organ-specific or cell-type-specific fashion? New approaches are required to answer these questions. The uses of the immunologically based in vivo antigen technology system, in situ PCR and DNA microarray analysis are considered. This review considers existing methods for examining bacterial gene expression in vivo, and describes emerging approaches that should further our understanding in the future.

Animals↗
PubMed2004

DNA microarray analysis of genome dynamics in Yersinia pestis: insights into bacterial genome microevolution and niche adaptation.

Genomics research provides an unprecedented opportunity for us to probe into the pathogenicity and evolution of the world's most deadly pathogenic bacterium, Yersinia pestis, in minute detail. In our present work, extensive microarray analysis in conjunction with PCR validation revealed that there are considerable genome dynamics, due to gene acquisition and loss, in natural populations of Y. pestis. We established a genomotyping system to group homologous isolates of Y. pestis, based on profiling or gene acquisition and loss in their genomes, and then drew an outline of parallel microevolution of the Y. pestis genome. The acquisition of a number of genomic islands and plasmids most likely induced Y. pestis to evolve rapidly from Yersinia pseudotuberculosis to a new, deadly pathogen. Horizontal gene acquisition also plays a key role in the dramatic evolutionary segregation of Y. pestis lineages (biovars and genomovars). In contrast to selective genome expansion by gene acquisition, genome reduction occurs in Y. pestis through the loss of DNA regions. We also theorized about the links between niche adaptation and genome microevolution. The transmission, colonization, and expansion of Y. pestis in the natural foci of endemic plague are parallel and directional and involve gradual adaptation to the complex of interactions between the environment, the hosts, and the pathogen itself. These adaptations are based on the natural selections against the accumulation of genetic changes within genome. Our data strongly support that the modern plague originated from Yunnan Province in China, due to the arising of biovar orientalis from biovar antiqua rather than mediaevalis.

Adaptation, Physiological↗
PubMed1998

DNA sequence sampling of the Streptococcus pneumoniae genome to identify novel targets for antibiotic development.

We initiated a survey of the Streptococcus pneumoniae genome by DNA sequence sampling. More than 9,500 random DNA sequences of approximately 500 bases average length were determined. Partial sequences sufficient to identify approximately 95% of the aminoacyl tRNA synthetase genes and ribosomal protein (rps) genes were found by comparing the database of partial sequences to known sequences from other organisms. Many genes involved in DNA replication, repair, and mutagenesis are present in S. pneumoniae. Genes for the major subunits of RNA polymerase are also present, as are genes for two alternative sigma factors, rpoD and rpoN. Many genes necessary for amino acid or cofactor biosynthesis and aerobic energy metabolism in other bacteria appear to be absent from the S. pneumoniae genome. A number of genes involved in cell wall biosynthesis and septation were identified, including six homologs to different penicillin binding proteins. Interestingly, four genes involved in the addition of D-alanine to lipoteicoic acid in other gram positive bacteria were found, even though the lipoteicoic acid in S. pneumoniae has not been shown to contain D-alanine. The S. pneumoniae genome contains a number of chaperonin genes similar to those found in other bacteria, but apparently does not contain genes involved in the type III secretion commonly observed in gram negative pathogens. The G+C content of S. pneumoniae genomic DNA is approximately 43 mole percent and the size of the genome is approximately 2.0 Mb as determined by pulsed-field gel electrophoresis. Many of the genes identified by sequence sampling have been physically mapped to the 19 different SmaI fragments derived from the S. pneumoniae genome. The database of random genome sequence tags (GSTs) provides the starting material for determining the complete genome sequence, gene disruption analysis, and comparative genomics to identify novel targets for antibiotic development.

Amino Acyl-tRNA Synthetases↗
PubMed2002

Genomic islands in Photorhabdus.

Genomic islands are responsible for unique aspects of bacterial behavior such as symbiosis and pathogenicity. Photorhabdus luminescens is a pathogen of insects that spends part of its lifecycle in symbiosis with a nematode. Here, we describe novel genomic islands from Photorhabdus that are involved in symbiosis and pathogenicity, and discuss the inter-relationship between virulence factors used against invertebrates and vertebrates.

Amino Acid Sequence↗
PubMed2026

Blau syndrome initially presenting with hypercalcemia: a case report and literature review.

Blau syndrome is a rare granulomatous autoinflammatory disease typically characterized by a triad of polyarthritis, uveitis, and dermatitis. It is caused by either an inherited autosomal dominant pathogenic variant or a de novo pathogenic variant in NOD2. In this report, we present an 11-month-old boy with Blau syndrome who initially presented with calcitriol-mediated hypercalcemia. Severe hypercalcemia was controlled with intravenous fluids, diuretics, calcitonin, and a short course of corticosteroids. Following resolution of the hypercalcemic episode, the patient gradually developed the full clinical spectrum of Blau syndrome, including the classic triad, along with hepatosplenomegaly, lymphadenopathy, and bone marrow involvement. Trio genome sequencing identified a de novo heterozygous pathogenic variant in NOD2. Following the genetic diagnosis, corticosteroids and methotrexate were initiated to control the disease. This is the first reported case of Blau syndrome presenting with hypercalcemia as an initial manifestation, preceding the development of the classic triad. This case underscores the importance of considering Blau syndrome in the differential diagnosis of early-onset hypercalcemia of unknown etiology. Molecular genetic testing should be pursued in such cases to facilitate an accurate and timely diagnosis and appropriate management.

Autoinflammatory disease↗
PubMed1982

Tree shrew (Tupaia) herpesviruses.

Five Tupaia herpesviruses have been isolated until now: four in our laboratory which were termed THV-2, 3, 4, and 5, whereas THV-1 has been isolated by Melnick and his colleagues. THV-2 was isolated from tumour cell culture of a high-grade malignant lymphoma of a Tupaia, THV-3 was released from a cell culture of another Tupaia lymphoma, THV-4 from a spleen tissue culture of a moribund animal with finely granulated liver cirrhosis, and THV-5 from cultured spleen cells of an apparently healthy tree shrew. THV-1 to 5 were efficiently propagated, plaque-purified and cloned on Tupaia embryonic fibroblasts. The five isolates of Tupaia herpesviruses are easily distinguished from each other by restriction enzyme analysis of their genomes. THV-1 to 4 are highly pathogenic (lethality 100%) for juvenile Tupaias by intravenous inoculation. In contrast, only 25% lethality was found by intraperitoneal administration. THV-1 to 4 can persist as a latent infection in spleens of Tupaias and rabbits, which allows the recovery of infectious virus from cultured spleens of both animals. THV-2 and 3 induced hyperplasia of the thymus of rabbits which developed malignant thymoma in a few cases. The biological properties and genomic size and structure indicate that THV cannot be considered to belong to one of the three existing subfamilies of herpesviruses.

Animals↗
PubMed2002

H. influenzae Consortium: integrative study of H. influenzae-human interactions.

Developments in high-throughput analysis tools coupled with integrative computational techniques have enabled biological studies to reach new levels. The ability to correlate large volumes of diverse data types into cohesive models of organism function has spawned a new systematic approach to biological investigation. The creation of a new consortium has been proposed to investigate a single organism utilizing these comprehensive approaches. The Haemophilus influenzae Consortium (HIC) would be comprised of five laboratories, each providing separate and complementary areas of expertise in the study of Haemophilus influenzae (HI). The 5-year study proposes to develop coherent models of HI, both as a stand-alone organism, and more importantly, as a human pathogen. Studies in growth condition specificity followed by genomic, metabolic, and proteomic experimentation will be combined and integrated through computational and experimental analyses to form dynamic and predictive models of HI and its responses. Data from the HIC will allow greater understanding of cellular behavior, pathogen-host interactions, bacterial infection, and provide future scientific endeavors with a template for studies of other pathogens.

Bacterial Adhesion↗
PubMed1992

A DNA probe specific to pathogenic Entamoeba histolytica.

A DNA sequence, IE-gen1 (3.1 kb), was isolated from the pathogenic strain of E. histolytica NIH-200. IE-gen1 was identified by the subtractive hybridization of a genomic library to a cDNA probe prepared from NIH-200 trophozoites. The IE-gen1 probe specifically detected pathogenic E. histolytica in slot blots of genomic DNA and Northern blots, but not other Entamoeba species and additional human parasites. This genomic probe could detect with complete specificity DNA from about 10(3) organisms. The IE-gen1 probe could be related to highly specialized loci in pathogenic E. histolytica, and is likely to be a valuable DNA reagent for clinical diagnosis and epidemiological investigations.

Animals↗
PubMed2004

Global transposon mutagenesis and essential gene analysis of Helicobacter pylori.

We have constructed a genome-saturating mutant library of the human gastric pathogen Helicobacter pylori. Microarray tracking of transposon mutants (MATT) allowed us to map the position of 5,363 transposon mutants in our library. While we generally found insertions well distributed throughout the genome, 344 genes had no detectable transposon insertions, and this list is predicted to be highly enriched for essential genes. Comparison to the essential gene set of other bacteria revealed a surprisingly limited overlap with all organisms tested (11%), while 55% were essential in some organisms but not others. We independently verified the essentiality of several gene products, including an HtrA family serine protease, a hypothetical protein with putative phospholipase D activity, and a riboflavin specific deaminase. A limited screen for motility mutants allowed us to estimate that 4.5% of the genome is dedicated to this virulence-associated phenotype.

Base Sequence↗
PubMed1991

[The effect of the bacterial genome on the expression and behavior of the plasmid determining the Ca2+-dependence of the plague pathogen].

The conjugative cointegrate containing the 47 Md plasmid of Yersinia pestis has been transferred into the strains of the different Yersinia (Yersinia pestis, Yersinia pseudotuberculosis, Yersinia enterocolitica) and Escherichia coli CA. There appeared in the populations of recombinant Yersinia under the conditions of Ca2+ deficit at 37 degrees C the cells coming into the stasis stage or dying. It was shown on the model of Yersinia enterocolitica that bacterial lethality might be prevented by exclusion of the sheep blood from Ca2+ deficient medium. Ca(2+)-dependence was not expressed in Escherichia coli cells in which the cointegrates were prone to deletions although the cad-genes were preserved intact. The latter conclusion is based on the positive reciprocal transfer of the Cad(+)-marker into Yersinia pestis cells.

Calcium↗
PubMed2005

Identification of pathogen-specific genes through microarray analysis of pathogenic and commensal Neisseria species.

The release of the complete genome sequences of Neisseria meningitidis MC58 and Z2491 along with access to the sequences of N. meningitidis FAM18 and Neisseria gonorrhoeae FA1090 allowed the construction of a pan-Neisseria microarray, with every gene in all four genomes represented. The microarray was used to analyse a selection of strains including all N. meningitidis serogroups and commensal Neisseria species. For each strain, genes were defined as present, divergent or absent using gack analysis software. Comparison of the strains identified genes that were conserved within N. meningitidis serogroup B strains but absent from all commensal strains tested, consisting of mainly virulence-associated genes and transmissible elements. The microarray was able to distinguish between pilin genes, pilC orthologues and serogroup-specific capsule biosynthetic genes, and to identify dam and drg genotypes. Previously described N. meningitidis genes involved in iron response, adherence to epithelial cells, and pathogenicity were compared to the microarray analysis. The microarray data correlated with other genetic typing methods and were able to predict genotypes for uncharacterized strains and thus offer the potential for a rapid typing method. The subset of pathogen-specific genes identified represents potential drug or vaccine targets that would not eliminate commensal neisseriae and the associated naturally acquired immunity.

Antigens, Bacterial↗
PubMed2005

Genome characterization of a flexuous rod-shaped mycovirus, Botrytis virus X, reveals high amino acid identity to genes from plant 'potex-like' viruses.

This study reports the molecular characterization of a flexuous rod-shaped mycovirus, Botrytis virus X (BVX), infecting the plant-pathogenic fungus, Botrytis cinerea. BVX contains a ssRNA genome of 6966 nucleotides, and a poly(A) tract at or very near the 3' terminus. Computer analysis of the genomic cDNA sequence of BVX revealed five potential open reading frames (ORFs). ORF1 showed significant amino acid sequence identity to the replicase proteins of plant 'potex-like' viruses, including 73% identity to the RNA-dependent RNA polymerase (RdRp) region of the allexivirus, garlic virus A (GarV-A). The C-terminal region of ORF3 shared amino acid homology with plant 'potex-like' coat proteins. The remaining ORFs did not reveal significant homology with known protein sequences. BVX differs substantially from Botrytis virus F (BVF), another flexuous rod-shaped mycovirus characterized from the same B. Cinerea isolate. It is proposed that the mycovirus BVX belongs to a new, as yet unassigned genus in the plant 'potex-like' virus group, distinct from BVF.

Amino Acid Sequence↗
PubMed1992

Construction of an EcoRI restriction map of Mycoplasma pneumoniae and localization of selected genes.

A restriction map of the genome of Mycoplasma pneumoniae, a small human pathogenic bacterium, was constructed by means of an ordered cosmid library which spans the complete bacterial chromosome. The positions of 143 endonuclease EcoRI restriction fragments were determined and aligned with the physical map. In addition, restriction sites for the rare-cutting enzymes XhoI (25 sites), ApaI (13 sites), NotI (2 sites), and SfiI (2 sites) were included. The resulting map consists of 185 restriction sites, has a mean resolution of 4.4 kbp, and predicts a genome size of 809 kbp. In addition, several genes were identified and mapped to their respective genomic EcoRI restriction fragments.

Amino Acid Sequence↗
PubMed2007

Comparative genomic analysis of prion genes.

BACKGROUND: The homologues of human disease genes are expected to contribute to better understanding of physiological and pathogenic processes. We made use of the present availability of vertebrate genomic sequences, and we have conducted the most comprehensive comparative genomic analysis of the prion protein gene PRNP and its homologues, shadow of prion protein gene SPRN and doppel gene PRND, and prion testis-specific gene PRNT so far. RESULTS: While the SPRN and PRNP homologues are present in all vertebrates, PRND is known in tetrapods, and PRNT is present in primates. PRNT could be viewed as a TE-associated gene. Using human as the base sequence for genomic sequence comparisons (VISTA), we annotated numerous potential cis-elements. The conserved regions in SPRNs harbour the potential Sp1 sites in promoters (mammals, birds), C-rich intron splicing enhancers and PTB intron splicing silencers in introns (mammals, birds), and hsa-miR-34a sites in 3'-UTRs (eutherians). We showed the conserved PRNP upstream regions, which may be potential enhancers or silencers (primates, dog). In the PRNP 3'-UTRs, there are conserved cytoplasmic polyadenylation element sites (mammals, birds). The PRND core promoters include highly conserved CCAAT, CArG and TATA boxes (mammals). We deduced 42 new protein primary structures, and performed the first phylogenetic analysis of all vertebrate prion genes. Using the protein alignment which included 122 sequences, we constructed the neighbour-joining tree which showed four major clusters, including shadoos, shadoo2s and prion protein-likes (cluster 1), fish prion proteins (cluster 2), tetrapode prion proteins (cluster 3) and doppels (cluster 4). We showed that the entire prion protein conformationally plastic region is well conserved between eutherian prion proteins and shadoos (18-25% identity and 28-34% similarity), and there could be a potential structural compatibility between shadoos and the left-handed parallel beta-helical fold. CONCLUSION: It is likely that the conserved genomic elements identified in this analysis represent bona fide cis-elements. However, this idea needs to be confirmed by functional assays in transgenic systems.

3' Untranslated Regions↗
PubMed2006

Integrated regulation of the type III secretion system and other virulence determinants in Ralstonia solanacearum.

In many plant and animal bacterial pathogens, the Type III secretion system (TTSS) that directly translocates effector proteins into the eukaryotic host cells is essential for the development of disease. In all species studied, the transcription of the TTSS and most of its effector substrates is tightly regulated by a succession of consecutively activated regulators. However, the whole genetic programme driven by these regulatory cascades is still unknown, especially in bacterial plant pathogens. Here, we have characterised the programme triggered by HrpG, a host-responsive regulator of the TTSS activation cascade in the plant pathogen Ralstonia solanacearum. We show through genome-wide expression analysis that, in addition to the TTSS, HrpG controls the expression of a previously undescribed TTSS-independent pathway that includes a number of other virulence determinants and genes likely involved in adaptation to life in the host. Functional studies revealed that this second pathway co-ordinates the bacterial production of plant cell wall-degrading enzymes, exopolysaccharide, and the phytohormones ethylene and auxin. We provide experimental evidence that these activities contribute to pathogenicity. We also show that the ethylene produced by R. solanacearum is able to modulate the expression of host genes and can therefore interfere with the signalling of plant defence responses. These results provide a new, integrated view of plant bacterial pathogenicity, where a common regulator activates synchronously upon infection the TTSS, other virulence determinants and a number of adaptive functions, which act co-operatively to cause disease.

Adaptation, Physiological↗
PubMed2006

Genomic rearrangements in MSH2, MLH1 or MSH6 are rare in HNPCC patients carrying point mutations.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease with high penetrance, caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, PMS2 and MLH3. Most reported pathogenic mutations are point mutations, comprising single base substitutions, small insertions and deletions. In addition, genomic rearrangements, such as large deletions and duplications not detectable by PCR and Sanger sequencing, have been identified in a significant proportion of HNPCC families, which do not carry a pathogenic MMR gene point mutation. To clarify whether genomic rearrangements in MLH1, MSH2 or MSH6 also occur in patients carrying a point mutation, we subjected normal tissue DNA of 137 colorectal cancer (CRC) patients to multiplex ligation-dependent probe amplification (MLPA) analysis. Patients fulfilled the following pre-requisites: all patients met at least one criterion of the Bethesda guidelines and their tumors exhibited high microsatellite instability (MSI-H) and/or showed loss of expression of MLH1, MSH2 or MSH6 proteins. PCR amplification and Sanger sequencing of all exons of at least one MMR gene, whose protein expression had been lost in the tumor tissue, identified 52 index patients without a point mutation (Group 1), 71 index patients with a pathogenic point mutation in MLH1 (n=38) or MSH2 (n=22) or MSH6 (n=11) (Group 2) and 14 patients with an unclassified variant in MLH1 (n=9) or MSH2 (n=3) or MSH6 (n=2) (Group 3). In 13 of 52 patients of group 1 deletions of at least one exon were identified. In addition, in group 3 one EX1_15del in MLH1 was found. No genomic rearrangement was identified in group 2 patients. Genomic rearrangements represent a significant proportion of pathogenic mutations of MMR genes in HNPCC patients. However, genomic rearrangements are rare in patients carrying point mutations in MMR genes. These findings suggest the use of genomic rearrangement tests in addition to Sanger sequencing in HNPCC patients.

Adaptor Proteins, Signal Transducing↗
PubMed1992

Molecular economy and antibody function: the evolution of a Protecton.

The humoral immune response protects against a very large array of pathogens which attempt to escape immune recognition by changing the antigens they display. When looked at from the point of two competing sets of DNA (i.e., the pathogens vs. the host), there is a vastly larger pool of mutating pathogen DNA than in, say, a mouse. The stratagems that allow a tiny fraction of the mouse's genome to effectively compete with a hugely diverse array of pathogens is analyzed in terms of how antibody functions and how the immune system avoids such pitfalls as self-recognition and destruction. This review is a more general description of a lengthy series of papers which detailed the evolution of the Protecton. Starting from the obvious, that is the concentration-dependence of antibody function, it is apparent that the functional antibody repertoire must be relatively small if a sufficient concentration of specific antibody is to be produced in time to arrest the growth of pathogens and eventually eliminate them. Thus, commonly quoted estimates of antibody repertoires in the range from greater than 10(10) to "complete" (infinite?) must be seriously in error. Other well known "facts", such as D-diversity, and B cell signaling by receptor aggregation are also shown to be lacking in biological commonsense.

Animals↗