Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pathogen genomics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,171 records · Page 65Linked to original sources
PubMed2000

DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.

Here we determine the complete genomic sequence of the gram negative, gamma-Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp). The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp that together encode 3,885 open reading frames. The vast majority of recognizable genes for essential cell functions (such as DNA replication, transcription, translation and cell-wall biosynthesis) and pathogenicity (for example, toxins, surface antigens and adhesins) are located on the large chromosome. In contrast, the small chromosome contains a larger fraction (59%) of hypothetical genes compared with the large chromosome (42%), and also contains many more genes that appear to have origins other than the gamma-Proteobacteria. The small chromosome also carries a gene capture system (the integron island) and host 'addiction' genes that are typically found on plasmids; thus, the small chromosome may have originally been a megaplasmid that was captured by an ancestral Vibrio species. The V. cholerae genomic sequence provides a starting point for understanding how a free-living, environmental organism emerged to become a significant human bacterial pathogen.

Base Sequence↗
PubMed2005

Targeted mutational analysis of ankyrin-B in 541 consecutive, unrelated patients referred for long QT syndrome genetic testing and 200 healthy subjects.

BACKGROUND: Mutations in ANK2-encoded ankyrin-B underlie long QT syndrome type 4 (LQT4) and various other dysrhythmia phenotypes. OBJECTIVES: The purpose of this study was to determine the prevalence and spectrum of ankyrin-B mutations in a large cohort of unrelated patients referred for LQTS genetic testing and among healthy control subjects. METHODS: Between August 1997 and July 2004, 541 consecutive, unrelated patients (358 females, average age at diagnosis 24 years, average QTc 482 ms) were referred to Mayo Clinic's Sudden Death Genomics Laboratory for comprehensive mutational analysis of the five cardiac channel genes implicated in LQTS: KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6). Based on this prior analysis, 269 of 541 cases lacked an identifiable mutation (genotype negative). In this study, targeted mutational analysis of 10 ANK2 exons (36,37,39-46) encoding the critical C-terminal regulatory domain or implicated previously as hosting pathogenic mutations was performed on genomic DNA from 541 patients and 200 control subjects using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing. RESULTS: Overall, 14 distinct nonsynonymous variants (10 novel) were observed in 9 (3.3%) of 269 genotype-negative LQTS patients, 5 (1.8%) of 272 genotype-positive LQTS cases, 4 (4%) of 100 white controls, and 9 (9%) of 100 black controls. Four variants found in controls (L1622I, T1626N, R1788W, and E1813K) were implicated previously as LQT4-associated mutations and displayed functional perturbations in vitro. All genotype-negative LQTS cases hosting ANK2 variants had been diagnosed as "atypical" or "borderline" cases, most presenting with normal QTc, nonexertional syncope, U waves, and/or sinus bradycardia. CONCLUSION: Nonsynonymous ankyrin-B variants were detected in nearly 3% of unrelated LQTS patients and nearly 7% of healthy control subjects. Genotype-negative LQTS patients with a single ANK2 variant displayed nonexertional syncope, U waves, sinus bradycardia, and extracardiac findings. Whether the identification of previously reported functionally significant variants residing in 2% of apparently healthy subjects suggests proarrhythmic potential or potential misclassification warrants further scrutiny.

Adolescent↗
PubMed2006

Isolation and sequencing of a temperate transducing phage for Pasteurella multocida.

A temperate bacteriophage (F108) has been isolated through mitomycin C induction of a Pasteurella multocida serogroup A strain. F108 has a typical morphology of the family Myoviridae, presenting a hexagonal head and a long contractile tail. F108 is able to infect all P. multocida serogroup A strains tested but not those belonging to other serotypes. Bacteriophage F108, the first P. multocida phage sequenced so far, presents a 30,505-bp double-stranded DNA genome with cohesive ends (CTTCCTCCCC cos site). The F108 genome shows the highest homology with those of Haemophilus influenzae HP1 and HP2 phages. Furthermore, an F108 prophage attachment site in the P. multocida chromosome has been established to be inside a gene encoding tRNA(Leu). By using several chromosomal markers that are spread along the P. multocida chromosome, it has been demonstrated that F108 is able to perform generalized transduction. This fact, together with the absence of pathogenic genes in the F108 genome, makes this bacteriophage a valuable tool for P. multocida genetic manipulation.

Animals↗
PubMed2005

The future of animal models of invasive aspergillosis.

The diagnosis of invasive aspergillosis remains very difficult, coupled with limited treatment options. Animal models have been utilized to evaluate both the diagnosis and treatment of infection and to assess the pathogenicity and virulence of the organism. However, animal models have not been standardized and have been used in only a limited fashion for genomic evaluation in this disease. Extensive efforts are underway to expand significantly the Aspergillus genomic information. Thus, the standardization of animal models of invasive aspergillosis is critical to create a unified platform to enhance evaluation of newer genomic information and allow assessment of pathogenicity and virulence factors. Proposed models, supported by a recently awarded National Institutes of Health/National Institute of Allergy and Infectious Diseases contract, will be developed in close interaction with the extended Aspergillus community (including academia and industry) to answer key questions in this disease. The goal of this work is to provide the framework to evaluate genomic targets in animal models in order to improve the diagnosis and treatment of invasive aspergillosis that will ultimately result in improved outcomes of patients with this frequently fatal infection.

Animals↗
PubMed2006

Ultrastructure and gliding motility of Mycoplasma amphoriforme, a possible human respiratory pathogen.

Despite their small size and reduced genomes, many mycoplasma cells have complex structures involved in virulence. Mycoplasma pneumoniae has served as a model for the study of virulence factors of a variety of mycoplasma species that cause disease in humans and animals. These cells feature an attachment organelle, which mediates cytadherence and gliding motility and is required for virulence. An essential component of the architecture of the attachment organelle is an internal detergent-insoluble structure, the electron-dense core. Little information is known regarding its underlying mechanisms. Mycoplasma amphoriforme, a close relative of both M. pneumoniae and the avian pathogen Mycoplasma gallisepticum, is a recently discovered organism associated with chronic bronchitis in immunosuppressed individuals. This work describes both the ultrastructure of M. amphoriforme strain A39(T) as visualized by scanning electron microscopy and the gliding motility characteristics of this organism on glass. Though externally resembling M. gallisepticum, M. amphoriforme cells were found to have a Triton X-100-insoluble structure similar to the M. pneumoniae electron-dense core but with different dimensions. M. amphoriforme also exhibited gliding motility using time-lapse microcinematography; its movement was slower than that of either M. pneumoniae or M. gallisepticum.

Humans↗
PubMed2003

Detection of somatic phages, infectious enteroviruses and enterovirus genomes as indicators of human enteric viral pollution in surface water.

In the present study, we aimed to determine whether the concentrations of somatic coliphages, infectious enteroviruses or the detection of enterovirus genomes were associated with the detection of human pathogenic viruses in surface water. Four French rivers were sampled monthly or semimonthly for the quantitative detection of somatic coliphages, infectious enteroviruses and the qualitative RT-PCR detection of enterovirus, hepatitis A virus, Norwalk I viruses, Norwalk II viruses, astrovirus and rotavirus genomes over 12 months. All the 68 water samples tested were positive for the quantitative detection of somatic coliphages (range of concentrations: 4 x 10(2) to 1.6 x10(5) FUl(-1)). Infectious enteroviruses were isolated by a cell culture system in only two (3%) of the 68 concentrated water samples tested, whereas enterovirus genomes were detectable in 60 (88%) of the same samples. A positive RT-PCR detection of the genome of hepatitis A virus, Norwalk-like virus genogroup II, astrovirus, rotavirus and Norwalk-like virus genogroup I was demonstrated, respectively, in 1.5% (1/68), 1.5% (1/68), 3% (2/68), 0% and 0% of the 68 concentrated water samples tested. All of these four water samples were positive for the detection of enterovirus genomes, whereas only one of them was positive for the isolation of enteroviruses on cell culture. Moreover, the genomic detection of human pathogenic viruses appeared not to be statistically associated with the concentration levels of somatic coliphages in the 68 concentrated water samples tested (Wilcoxon rank test; P=0.14). Taken together, our findings indicate that the quantitative detection of somatic coliphages and the isolation of enteroviruses on cell culture are not suitable parameters for the control of the viral contamination in surface water, whereas the detection of enterovirus genomes may be useful for predicting the presence of waterborne viruses.

Cell Culture Techniques↗
PubMed2026

Large-scale discovery platform enables identification of peptides targeting drug-resistant candidiasis.

Natural products have an unparalleled track record as sources of clinical drugs. Among them, nonribosomal peptides (NRPs) stand as one of the most therapeutically significant classes, encompassing numerous approved anti-infective and anticancer agents. Yet, discovering bioactive NRPs remains profoundly challenging due to their complex biosynthesis and chemical architecture. Here, we present NPDiscover, a pathogen-oriented, scalable bioinformatics platform that integrates genome mining, metabolomics, and machine learning to identify NRPs active against drug-resistant pathogens. Applying NPDiscover to Actinobacteria datasets, we discovered edaphochelin A, a previously unreported NRP that kills multi-drug-resistant Candida auris and Candida glabrata by disrupting respiratory chain proteins. Structural elucidation via nuclear magnetic resonance and mass spectrometry, alongside in vitro and in vivo validation, confirmed its efficacy, safety, and a mode of action distinct from existing antifungals-establishing edaphochelin A as a compelling drug candidate and NPDiscover as a powerful engine for scalable natural product discovery.

CP: biotechnology↗
PubMed2005

CandidaDB: a genome database for Candida albicans pathogenomics.

CandidaDB is a database dedicated to the genome of the most prevalent systemic fungal pathogen of humans, Candida albicans. CandidaDB is based on an annotation of the Stanford Genome Technology Center C.albicans genome sequence data by the European Galar Fungail Consortium. CandidaDB Release 2.0 (June 2004) contains information pertaining to Assembly 19 of the genome of C.albicans strain SC5314. The current release contains 6244 annotated entries corresponding to 130 tRNA genes and 5917 protein-coding genes. For these, it provides tentative functional assignments along with numerous pre-run analyses that can assist the researcher in the evaluation of gene function for the purpose of specific or large-scale analysis. CandidaDB is based on GenoList, a generic relational data schema and a World Wide Web interface that has been adapted to the handling of eukaryotic genomes. The interface allows users to browse easily through genome data and retrieve information. CandidaDB also provides more elaborate tools, such as pattern searching, that are tightly connected to the overall browsing system. As the C.albicans genome is diploid and still incompletely assembled, CandidaDB provides tools to browse the genome by individual supercontigs and to examine information about allelic sequences obtained from complementary contigs. CandidaDB is accessible at http://genolist.pasteur.fr/CandidaDB.

Candida albicans↗
PubMed2001

Identification and characterization of variable-number tandem repeats in the Yersinia pestis genome.

Yersinia pestis, the infamous plague-causing pathogen, appears to have emerged in relatively recent history. Evidence of this fact comes from several studies that document a lack of nucleotide diversity in the Y. pestis genome. In contrast, we report that variable-number tandem repeat (VNTR) sequences are common in the Y. pestis genome and occur frequently in gene coding regions. Larger tandem repeat arrays, most useful for phylogenetic analysis, are present at an average of 2.18 arrays per 10 kbp and are distributed evenly throughout the genome and the two virulence plasmids, pCD1 and pMT1. We examined allelic diversity at 42 chromosomal VNTR loci in 24 selected isolates (12 globally distributed and 12 from Siskiyou County, Calif.). Vast differences in diversity were observed among the 42 VNTR loci, ranging from 2 to 11 alleles. We found that the maximum copy number of repeats in an array was highly correlated with diversity (R = 0.86). VNTR-based phylogenetic analysis of the 24 strains successfully grouped isolates from biovar orientalis and most of the antiqua and mediaevalis strains. Hence, multiple-locus VNTR analysis (MLVA) appears capable of both distinguishing closely related strains and successfully classifying more distant relationships. Harnessing the power of MLVA to establish standardized databases will enable researchers to better understand plague ecology and evolution around the world.

Animals↗
PubMed2004

Genome-based vaccines.

Vaccination is an effective possibility to prevent many bacterial or viral infections, but for several important pathogens still no vaccines are available. The sequences of complete genomes are now decoded for an increasing number of bacterial pathogens and offer the possibility for comprehensive screenings to identify targets for vaccine development. In this article current genomic approaches to identify antigenic proteins of Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus aureus, and Chlamydia pneumoniae are summarized.

Antigens, Bacterial↗
PubMed2026

Three thousand five hundred years of sheeppox virus evolution inferred from archaeological and codicological genomes.

Sheeppox virus (SPPV) is a major livestock pathogen causing economic hardship through reduced production and death of vulnerable sheep, with written descriptions of sheeppox-like disease recorded since antiquity. We report 21 novel ancient SPPV genomes spanning the Eurasian steppe Bronze Age (∼1700 BCE) to the Early Modern period in Western Europe, including multiple genomes obtained from medieval parchment. We estimate that major capripoxvirus lineages diverged ∼11,500 to 3700 years ago, overlapping known translocations and bio-cultural developments in sheep. Our dataset supports SPPV diverging first within the lineage leading to goatpox virus and lumpy skin disease virus, and that known gene inactivation events within SPPV and goatpox virus occur in our earliest SPPV genomes. These findings reveal that the food security of Eurasian communities has been threatened by sheeppox for more than 3700 years and provide insights into the genomic evolution and potential host adaptation of SPPV.

Animals↗
PubMed2026

A New Threat Emerges: The First Detection of GVIII Genotype IBV in China and the Urgent Need for Molecular Surveillance.

In 2025, an infectious bronchitis virus (IBV) strain of the GVIII genotype was identified and isolated from a poultry farm in Hebei Province, China, representing the first documented detection of this IBV genotype within the country to date. Nucleotide homology analysis revealed that the S1 gene of this isolate shares 62.2%-96.9% sequence identity with previously reported GVIII-type strains from other countries. Comprehensive phylogenetic analysis of the complete genome indicated that this strain originated from a single recombination event: Its S gene may have been derived from the GVIII-1 lineage strain IBV/Ck/USA/CA/21-1883, while the remaining genomic regions were likely acquired from the GI-19 lineage strain SD. Pathogenicity evaluation demonstrated that infected flocks exhibited reduced body weight gain, with 40% of chickens showing signs of diarrhea. Necropsy findings included hemorrhagic lesions at the proventriculus-gizzard junction and within the bursa of Fabricius. Moreover, 85% of infected hens developed severe oviduct hypoplasia, and 90% showed a reduction in follicular number. The isolate described in this study constitutes the first detection of a GVIII genotype IBV strain in China, although its route of introduction remains undetermined. The emergence of this strain highlights the necessity for sustained molecular surveillance of IBV and the development of genotype-matched vaccines.

Animals↗
PubMed2003

The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus.

Helicobacter hepaticus causes chronic hepatitis and liver cancer in mice. It is the prototype enterohepatic Helicobacter species and a close relative of Helicobacter pylori, also a recognized carcinogen. Here we report the complete genome sequence of H. hepaticus ATCC51449. H. hepaticus has a circular chromosome of 1,799,146 base pairs, predicted to encode 1,875 proteins. A total of 938, 953, and 821 proteins have orthologs in H. pylori, Campylobacter jejuni, and both pathogens, respectively. H. hepaticus lacks orthologs of most known H. pylori virulence factors, including adhesins, the VacA cytotoxin, and almost all cag pathogenicity island proteins, but has orthologs of the C. jejuni adhesin PEB1 and the cytolethal distending toxin (CDT). The genome contains a 71-kb genomic island (HHGI1) and several genomic islets whose G+C content differs from the rest of the genome. HHGI1 encodes three basic components of a type IV secretion system and other virulence protein homologs, suggesting a role of HHGI1 in pathogenicity. The genomic variability of H. hepaticus was assessed by comparing the genomes of 12 H. hepaticus strains with the sequenced genome by microarray hybridization. Although five strains, including all those known to have caused liver disease, were indistinguishable from ATCC51449, other strains lacked between 85 and 229 genes, including large parts of HHGI1, demonstrating extensive variation of genome content within the species.

Cell Movement↗
PubMed2002

Linear plasmid in the genome of Clavibacter michiganensis subsp. sepedonicus.

Contour-clamped homogeneous electric field gel analysis of genomic DNA of the plant pathogen Clavibacter michiganensis subsp. sepedonicus revealed the presence of a previously unreported extrachromosomal element. This new element was demonstrated to be a linear plasmid. Of 11 strains evaluated, all contained either a 90-kb (pCSL1) or a 140-kb (pCSL2) linear plasmid.

DNA, Bacterial↗
PubMed1994

Genetic approaches to study Legionella pneumophila pathogenicity.

Legionella pneumophila is an intracellular pathogen replicating in human macrophages during the course of infection of the lungs. Infection by legionellae often leads to severe pneumonia, termed Legionnaires' disease. Genetic approaches to identify the factors responsible for L. pneumophila pathogenicity started with the construction of genomic libraries in Escherichia coli. Various L. pneumophila-specific genes were cloned in E. coli K-12 by identification using functional assays, antibody screening and hybridization ('reverse genetics'). By disrupting the genes via allelic exchange, mutants have been created to assess the influence of the factors on pathogenicity. Among the cloned genes, only for the gene product of the mip gene, encoding a 24-kDa surface-associated protein (macrophage infectivity potentiator) unequivocal evidence for its contribution to pathogenicity could be provided. Two hemolytic factors that have been cloned do not seem to play a role in L. pneumophila pathogenicity. Genetic systems for transposon mutagenesis of the L. pneumophila genome (Tn5, Tn903dIIlacZ, MudphoA), including Tn phoA shuttle mutagenesis, have been established and specifically adapted to identify mutants which displayed an impaired capability to multiply inside macrophages and with a reduced in vivo virulence. Furthermore, by complementation of avirulent mutants, genetic loci could be identified which restored the virulence.

Gene Expression Regulation, Bacterial↗
PubMed1995

Sequence of a gene encoding periplasmic Pseudomonas syringae ankyrin.

A gene encoding ankyrin (Ank) was isolated from a genomic library of the plant pathogen Pseudomonas syringae pathovar syringae strain 61 (Pss61). The gene encodes an 183-amino-acid (aa) polypeptide which has homology to the 33-aa repeat domain of mammalian Ank and Ank homologs from other bacteria, animals and plants.

Amino Acid Sequence↗
PubMed2005

An efficient algorithm for sorting by block-interchanges and its application to the evolution of vibrio species.

In the study of genome rearrangement, the block-interchanges have been proposed recently as a new kind of global rearrangement events affecting a genome by swapping two nonintersecting segments of any length. The so-called block-interchange distance problem, which is equivalent to the sorting-by-block-interchange problem, is to find a minimum series of block-interchanges for transforming one chromosome into another. In this paper, we study this problem by considering the circular chromosomes and propose a Omicron(deltan) time algorithm for solving it by making use of permutation groups in algebra, where n is the length of the circular chromosome and delta is the minimum number of block-interchanges required for the transformation, which can be calculated in Omicron(n) time in advance. Moreover, we obtain analogous results by extending our algorithm to linear chromosomes. Finally, we have implemented our algorithm and applied it to the circular genomic sequences of three human vibrio pathogens for predicting their evolutionary relationships. Consequently, our experimental results coincide with the previous ones obtained by others using a different comparative genomics approach, which implies that the block-interchange events seem to play a significant role in the evolution of vibrio species.

Algorithms↗
PubMed2006

Patho-biotechnology: using bad bugs to do good things.

Pathogenic bacteria have evolved sophisticated strategies to overcome host defences, to interact with the immune system and to interfere with essential host systems. We coin the term 'patho-biotechnology' to describe the exploitation of these valuable traits in biotechnology, medicine and food. This approach shows promise for the development of novel vaccine and drug delivery systems, as well as for the design of more technologically robust and effective probiotic cultures with improved biotechnological and clinical applications. The genetic tractability of Listeria monocytogenes, the availability of the complete genome sequence of this intracellular pathogen, its ability to cope with stress, and its ability to traverse the gastrointestinal tract and induce a strong cellular immune response make L. monocytogenes an ideal model organism for demonstrating the patho-biotechnology concept.

Animals↗