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At least 1,099 records · Page 61Linked to original sources
PubMed1995

Deletions and duplication in internal inverted repeat sequence of long region/unique sequence of long region (IRL/UL) of herpes simplex virus type-1 (HSV-1) genome are not evidently associated with intracranial and foot-pad pathogenicity in mouse model.

The biological properties of three deletion variants (1704, 1705 and 1706) of herpes simplex virus type-1 (HSV-1) strain 17 syn+, were studied by establishing a base line pathogenicity of nine individual plaques from the parental 17 syn+ elite stock. Restriction enzyme analysis of deoxyribonucleic acid (DNA) from each of the nine plaque stocks and intracranial inoculation into three weeks old BALB/c mice showed no difference in the size of fragments and distribution of the sites or their 50% lethal dose (LD50) values [plaque forming units (pfu)/mouse] as compared to the parental 17 syn+ stock. Inoculation of the variants into three weeks old BALB/c mice showed that 1705 was not different in pathogenicity from the wild type following intracranial and footpad inoculations. On the other hand variants 1704 and 1706, when compared to the wild type virus were less virulent on intracranial inoculation i.e. the difference in LD50 values was approximately one log and two logs respectively and both the variants failed to kill any of the animals following footpad inoculation even at the dose of 1 x 10(7) pfu/mouse. During in vivo replication experiment in the peripheral nervous system of mice, 1704 and 1706 grew very poorly.

Amino Acid Sequence↗
PubMed2007

Unit-length, single-stranded circular DNAs of both polarity of begomoviruses are generated in Escherichia coli harboring phage M13-cloned begomovirus genome with single copy of replication origin.

Replication of genomic DNAs of plant-pathogenic begomoviruses has been demonstrated in prokaryotes, which supported the possibility of analyzing DNA replication process of begomoviruses in bacteria. However, previous studies indicated that the replication of begomovirus DNAs in prokaryotes requires tandem constructs of viral genomes with at least two copies of the origin of replication (ori). In this study, phage M13 vector harboring the unit-length genome with only a single copy of ori of a mono-partite begomovirus, Ageratum yellow vein virus PD isolate (AYVV-[PD]), was constructed and used to investigate the replication of AYVV-[PD] DNAs in Escherichia coli. The generation of single-stranded, circular DNAs (sscDNAs) corresponding to the unit-length AYVV-[PD] genome of both polarity was observed and verified. Replication-associated (Rep) protein of AYVV-[PD] was detected only in bacteria generating the corresponding sscDNAs, whereas disruption of the Rep gene abolished the phenomenon. The results suggested that a single copy of ori is sufficient for the prokaryotes to support the generation of unit-length, genomic sscDNAs of begomoviruses, which requires the presence of functional Rep protein.

Bacteriophage M13↗
PubMed2001

Improved pattern for genome-based screening identifies novel cell wall-attached proteins in gram-positive bacteria.

With a large number of sequenced microbial genomes available, tools for identifying groups or classes of proteins have become increasingly important. Here we present an improved pattern for the identification of cell wall-attached proteins (CWPs), a group of proteins with diverse and important functions in gram-positive bacteria. This tripartite pattern is based on analysis of 65 previously described cell wall-attached proteins and takes into account the three principal requirements for cell wall sorting; a sortase target region (LPXTGX), a membrane-spanning region, and a charged stop-transfer tail. In five different genomes of gram-positive bacteria, the tripartite pattern identified a total of 35 putative CWPs, 19 of which were novel. The specificity and sensitivity of the tripartite pattern are higher than those of the classical pattern, which is based solely on the sortase target region. Several putative CWPs with atypical sortase target regions were identified. In the complete genome of the important human pathogen Streptococcus pyogenes, the tripartite pattern identified 14 putative CWPs. Seven of the putative S. pyogenes proteins were novel, and two of these were a 5' nucleotidase and a pullulanase. This study represents the first whole-genome screening for CWPs, and we conclude that the tripartite pattern is highly suitable for this purpose. Identification of CWPs using this pattern offers important possibilities in the study of the pathogenesis and physiology of gram-positive bacteria.

Amino Acid Sequence↗
PubMed1993

Homology between cryptic plasmid from Neisseria gonorrhoeae and genomic DNA from Neisseria meningitidis.

The human pathogenic Neisseria species N. gonorrhoeae and N. meningitidis are closely related. In contrast to N. meningitidis, however, almost all clinical isolates of N. gonorrhoeae harbour a phenotypically cryptic plasmid. In some gonococcal strains regions of the cryptic plasmid have been found in the gonococcal genome and it has been suggested that large segments of the cryptic plasmid can be integrated into the gonococcal chromosome of both plasmid-bearing and plasmid-free strains. Here we report homology between parts of the cryptic gonococcal plasmid and genomic DNA from four different N. meningitidis strains from systemic disease isolates in which no plasmids have been found with the applied methods. Serogroup B strains, causing many of the cases of meningococcal disease in Norway, hybridized strongly to the cryptic plasmid probe, in contrast to serogroup A and C strains. Clones hybridizing to the cryptic plasmid were isolated from a meningococcal genomic lambda EMBL3 DNA library and characterized by restriction mapping. When using one such clone as a probe the parts of the cryptic plasmid showing homology to the genomic meningococcal DNA were confined to two small separate regions of 420 and 88 bp.

DNA, Bacterial↗
PubMed1998

[Innovative new approaches in pharmacology].

After a brief recall of the molecular bases of the pharmacological actions, the two main ways of discovery of new drugs are described. On the one hand, the "deductive" approach starts with the elucidation of the pathogenic mechanisms and leads to selective drug designs for the appropriate receptors. The recent contributions of the molecular biology in this way are illustrated by some examples: "knock out" mice for the study of gene functions, discovery of new antibiotics thanks to genomic sequencing of bacteria, new pathogenic concepts about inflammation... On the other hand, the empirical approach is now grounded on two performant methods: High Throughput Screening and Combinatorial Chemistry which together have already given practical results. It is obvious that these two approaches are not opposite, but complementary.

Animals↗
PubMed2026

A tiled amplicon protocol for culture-free whole-genome sequencing of M. tuberculosis from clinical specimens.

Whole-genome sequencing of Mycobacterium tuberculosis can be a valuable tool for TB surveillance and treatment, providing insights into transmission patterns and comprehensive drug susceptibility testing. However, the slow growth of M. tuberculosis means traditional culture-based sequencing methods can take weeks to return results, which has limited the widespread adoption of these techniques and limited their use in clinical decision-making. Tiled amplicon sequencing is a fast, reliable, and cost-effective method of whole-genome sequencing that can be done directly on clinical specimens and has been implemented at scale in academic and public health laboratories across the world; it was the cornerstone of SARS-CoV-2 sequencing and has been adapted for a wide range of viral pathogens. However, similar methods are not yet available for far larger bacterial genomes. Extending this approach to M. tuberculosis would significantly reduce the cost, labor, and turnaround time for whole-genome sequencing. We designed a tiled amplicon panel consisting of 5,128 primers that covers the entire M. tuberculosis genome, the largest tiled amplicon sequencing panel we are aware of to date. Applying our amplicon panels to clinical samples of sputum, we show the ability to recover whole-genome bacterial sequences without the need for culture. The resulting sequence data can be used to determine M. tuberculosis lineage and reliably identify markers of drug resistance. Using this approach in clinical settings could reduce the time needed for comprehensive drug susceptibility testing from weeks to days and enable genomic epidemiology to be performed at scale, even in resource-limited settings.IMPORTANCEWe have developed and tested an amplicon panel, TB-seq, for the priority pathogen Mycobacterium tuberculosis, demonstrating recovery of near-full genomes directly from patient sputum, including mixed and low-concentration samples. This approach significantly reduces the turnaround time for this slow-growing bacterium while maintaining high accuracy in detecting clinically relevant mutations, including those associated with drug resistance. Given the global burden of tuberculosis and the critical need for faster diagnostic solutions, we believe our method has the potential to improve clinical decision-making and public health strategies.

Mycobacterium tuberculosis↗
PubMed2002

Cloning and expression of the haloalkane dehalogenase gene dhmA from Mycobacterium avium N85 and preliminary characterization of DhmA.

Haloalkane dehalogenases are microbial enzymes that catalyze cleavage of the carbon-halogen bond by a hydrolytic mechanism. Until recently, these enzymes have been isolated only from bacteria living in contaminated environments. In this report we describe cloning of the dehalogenase gene dhmA from Mycobacterium avium subsp. avium N85 isolated from swine mesenteric lymph nodes. The dhmA gene has a G+C content of 68.21% and codes for a polypeptide that is 301 amino acids long and has a calculated molecular mass of 34.7 kDa. The molecular masses of DhmA determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by gel permeation chromatography are 34.0 and 35.4 kDa, respectively. Many residues essential for the dehalogenation reaction are conserved in DhmA; the putative catalytic triad consists of Asp123, His279, and Asp250, and the putative oxyanion hole consists of Glu55 and Trp124. Trp124 should be involved in substrate binding and product (halide) stabilization, while the second halide-stabilizing residue cannot be identified from a comparison of the DhmA sequence with the sequences of three dehalogenases with known tertiary structures. The haloalkane dehalogenase DhmA shows broad substrate specificity and good activity with the priority pollutant 1,2-dichloroethane. DhmA is significantly less stable than other currently known haloalkane dehalogenases. This study confirms that a hydrolytic dehalogenase is present in the facultative pathogen M. avium. The presence of dehalogenase-like genes in the genomes of other mycobacteria, including the obligate pathogens Mycobacterium tuberculosis and Mycobacterium bovis, as well as in other bacterial species, including Mesorhizobium loti, Xylella fastidiosa, Photobacterium profundum, and Caulobacter crescentus, led us to speculate that haloalkane dehalogenases have some other function besides catalysis of hydrolytic dehalogenation of halogenated substances.

Alkanes↗
PubMed2025

Unraveling a novel FBN1 variant in Marfan syndrome with dilated aortic root manifestation.

BACKGROUND: Marfan syndrome (MFS) is a genetic disorder affecting connective tissue, with variable incidence rates. A significant portion of cases stems from novel genetic variants, while others inherit it from affected parents. OBJECTIVE: This study focuses on identifying the genetic cause of MFS in a specific family, using whole-exome sequencing (WES). METHODS: A 15-year-old male with confirmed MFS was examined, showing symptoms of palpitations and severe mitral valve regurgitation. WES was performed, followed by confirmation with Sanger sequencing. Variants were assessed for pathogenicity using bioinformatics tools and the American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: One potentially novel pathogenic variant was found in exon 14 of the FBN1 gene: c.1676delCinsAAT, p.Ala559GlufsTer21. In silico analysis suggested a deleterious impact on protein structure and function, supporting their pathogenic classification. CONCLUSION: The identification of this novel variant highlights the importance of the FBN1 gene in MFS, especially its cardiovascular manifestations. Early intervention can improve patient outcomes, while ongoing research holds promise for further advancements in treatment for Marfan syndrome.

Humans↗
PubMed2005

Hemipterans as plant pathogens.

Integration of the tools of genetics, genomics, and biochemistry has provided new approaches for identifying genes responding to herbivory. As a result, a picture of the complexity of plant-defense signaling to different herbivore feeding guilds is emerging. Plant responses to hemipteran insects have substantial overlap with responses mounted against microbial pathogens, as seen in changes in RNA profiles and emission of volatiles. Responses to known defense signals and characterization of the signaling pathways controlled by the first cloned insect R gene (Mi-1) indicate that perception and signal transduction leading to resistance may be similar to plant-pathogen interactions. Additionally, novel signaling pathways are emerging as important components of plant defense to insects. The availability of new tools and approaches will further enhance our understanding of the nature of defense in plant-hemipteran interactions.

Animals↗
PubMed2004

Putative lipoproteins of Streptococcus agalactiae identified by bioinformatic genome analysis.

Streptococcus agalactiae is a significant pathogen causing invasive disease in neonates and thus an understanding of the molecular basis of the pathogenicity of this organism is of importance. N-terminal lipidation is a major mechanism by which bacteria can tether proteins to membranes. Lipidation is directed by the presence of a cysteine-containing 'lipobox' within specific signal peptides and this feature has greatly facilitated the bioinformatic identification of putative lipoproteins. We have designed previously a taxon-specific pattern (G+LPP) for the identification of Gram-positive bacterial lipoproteins, based on the signal peptides of experimentally verified lipoproteins (Sutcliffe I.C. and Harrington D.J. Microbiology 148: 2065-2077). Patterns searches with this pattern and other bioinformatic methods have been used to identify putative lipoproteins in the recently published genomes of S. agalactiae strains 2603/V and NEM316. A core of 39 common putative lipoproteins was identified, along with 5 putative lipoproteins unique to strain 2603/V and 2 putative lipoproteins unique to strain NEM316. Thus putative lipoproteins represent ca. 2% of the S. agalactiae proteome. As in other Gram-positive bacteria, the largest functional category of S. agalactiae lipoproteins is that predicted to comprise of substrate binding proteins of ABC transport systems. Other roles include lipoproteins that appear to participate in adhesion (including the previously characterised Lmb protein), protein export and folding, enzymes and several species-specific proteins of unknown function. These data suggest lipoproteins may have significant roles that influence the virulence of this important pathogen.

Amino Acid Sequence↗
PubMed1995

Characterization of clinical isolates of Streptococcus agalactiae by random amplified polymorphic DNA using degenerate oligonucleotides.

Epidemiological studies of Streptococcus agalactiae strains have been limited by the lack of sensitive and discriminatory methods for comparing clinical isolates. Serotyping, albeit a widely used methodology, has been shown to possess low capability to distinguish between epidemiologically related and unrelated isolates. We have employed here a random amplification of polymorphic DNA (RAPD) assay, using degenerate oligonucleotides as primers, to characterize S. agalactiae isolates from related or unrelated clinical samples. Epidemiologically-related isolates (mother-infant pairs) showed identical profiles by this methodology. On the contrary, 12 epidemiologically-unrelated isolates (classified into 5 different serotypes) resulted in 11 distinct RAPD patterns. This suggests that the proposed modified RAPD assay provides a highly discriminatory tool for the analysis of genomic diversity among isolates from pathogenic organisms.

DNA Primers↗
PubMed1989

Molecular epidemiology and restriction site mapping of adenovirus 7 genome types.

From the United States, the Federal Republic of Germany, and other regions, 168 strains of AV7, isolated between 1961 and 1985, were analyzed by six restriction endonucleases and nine genome types were identified. The enzymes BamHI and HindIII were most discriminative. The genome type D5 (or 7b) predominated with 120 isolates since 1970 in both countries. Strains of D2 (7a) and D4 (7c) were isolated for a limited time, D3 for an extended time period. Several clusters of infections with the same genome type were found. Differences in pathogenicity could not be derived from our data. On the basis of restriction site mapping, most other genome types were similar to D5, one to D2 and one to the prototype (D1). The genomic relation between AV7 and AV3 is discussed and shown by a dendrogram.

Adenoviridae↗
PubMed2025

Characterization of a novel putative lantibiotic biosynthesis genomic island in emerging clones of Listeria monocytogenes serotype 4b.

Listeria monocytogenes is a Gram-positive facultative intracellular bacterium that is ubiquitous in nature and the causative agent of listeriosis. The outbreak-derived serotype 4b strain L. monocytogenes strain WS1, sequence type (ST) 558, sublineage (SL) 558, was previously found to have unusual pathogenicity, with ability to cause fetal damage in the first trimester of pregnancy. Search of the WS1 genome for novel and unique genomic features identified a putative lantibiotic island on the chromosome of WS1 and all tested strains of SL558 and two other putative emerging serotype 4b clones, clonal complex 554 (SL554 and SL555) and ST782 (SL782), but absent from all other major clones of L. monocytogenes. The island was deleted from four strains, including two each of ST558 and ST554. The deletions did not impact virulence in a Galleria mellonella model but consistently resulted in reduced hemolytic activity. In addition, we noted strain-dependent impacts on biofilm formation. Additional studies will be necessary to further elucidate the roles of this genomic island in the adaptive physiology and virulence of L. monocytogenes.

Listeria monocytogenes↗
PubMedDate not supplied

Proteomics and bioinformatics strategies to design countermeasures against infectious threat agents.

The potential devastation resulting from an intentional outbreak caused by biological warfare agents such as Brucella abortus and Bacillus anthracis underscores the need for next generation vaccines. Proteomics, genomics, and systems biology approaches coupled with the bacterial ghost (BG) vaccine delivery strategy offer an ideal approach for developing safer, cost-effective, and efficacious vaccines for human use in a relatively rapid time frame. Critical to any subunit vaccine development strategy is the identification of a pathogen's proteins with the greatest potential of eliciting a protective immune response. These proteins are collectively referred to as the pathogen's immunome. Proteomics provides high-resolution identification of these immunogenic proteins using standard proteomic technologies, Western blots probed with antisera from infected patients, and the pathogen's sequenced and annotated genome. Selected immunoreactive proteins can be then cloned and expressed in nonpathogenic Gram-negative bacteria. Subsequently, a temperature shift or chemical induction process is initiated to induce expression of the PhiX174 E-lysis gene, whose protein product forms an E tunnel between the inner and outer membrane of the bacteria, expelling all intracellular contents. The BG vaccine system is a proven strategy developed for many different pathogens and tested in a complete array of animal models. The BG vaccine system also has great potential for producing multiagent vaccines for protection to multiple species in a single formulation.

Bacillus anthracis↗
PubMed2000

Phytoplasma: phytopathogenic mollicutes.

During the past decade, research has yielded new knowledge about the plant and insect host ranges, geographical distribution, and phylogenetic relationships of phytoplasmas, and a taxonomic system has emerged in which distinct phytoplasmas are named as separate "Candidatus phytoplasma species." In large part, this progress has resulted from the development and use of molecular methods to detect, identify, and classify phytoplasmas. While these advances continue, research has recently begun on the phytoplasma genome, how phytoplasmas cause disease, the role of mixed phytoplasmal infections in plant diseases, and molecular/genetic phenomena that underlie symptom development in plants. These and other recent advances are laying the foundation for future progress in understanding the mechanisms of phytoplasma pathogenicity, organization of the phytoplasma genome, evolution of new phytoplasma strains and emergence of new diseases, bases of insect transmissibility and specificity of transmission, and plant gene expression in response to phytoplasmal infection, as well as the design of novel approaches to achieve effective control of phytoplasmal diseases.

Ecology↗
PubMed2026

Comparative genomic epidemiology of food- and patient-derived diarrheagenic Escherichia coli from sentinel surveillance in Southeast China.

Diarrheagenic Escherichia coli (DEC) remains an important foodborne pathogen, yet long-term comparative genomic surveillance data jointly characterizing food-derived and patient-derived isolates remain limited. This surveillance-based comparative study integrated antimicrobial susceptibility testing and whole-genome sequencing to characterize diarrheagenic Escherichia coli isolates recovered from food and patient sources in Lishui, Southeast China, during 2018-2025, with emphasis on occurrence, resistance profiles, genomic backgrounds, and plasmid replicon-associated features. Antimicrobial susceptibility testing was performed for 258 selected isolates, and whole-genome sequencing was conducted for a curated analytical subset of 204 isolates. The sequenced subset was used for diversity-oriented comparative genomic analysis rather than for unbiased prevalence estimation of the entire DEC collection. EAEC predominated in both sources, although food-associated occurrence was heterogeneous across categories, with the highest recovery rate observed in raw meat. Patient-derived isolates showed a broader overall resistance burden, whereas food-derived isolates retained substantial resistance to tetracycline, chloramphenicol, and florfenicol. Phylogenetic analysis showed partial overlap in genomic backgrounds between food-derived and patient-derived isolates, while representative resistance determinants displayed both broadly distributed and lineage-enriched patterns. Replicon-based plasmid profiling identified 42 plasmid types, including 12 detected in both sources, with IncF-related replicons predominating among these shared profiles. Several food-derived isolates carried multiple plasmid replicon types that were also observed in patient-derived isolates. Overall, food-derived and patient-derived DEC showed partial overlap in genomic backgrounds, resistance determinants, and replicon-defined plasmid profiles within this surveillance setting, while retaining source-associated heterogeneity. These findings should be interpreted as surveillance-based comparative evidence rather than as evidence of direct source attribution or transmission.

Humans↗
PubMed1992

The pathogenicity of Ab4p, the sequenced strain of equine herpesvirus-1, in specific pathogen-free foals.

The sequencing of the genome of equine herpesvirus-1 (EHV-1) is reported in Elizabeth A. R. Telford, Moira S. Watson, Kathryn McBride, and Andrew J. Davison, 1992, Virology, 189, 304-316. The sequence was derived using a plaque-purified clone of EHV-1 strain Ab4 (designated Ab4p). To ensure that Ab4p shares the pathogenic characteristics of parental Ab4 (hereafter Ab4), both were inoculated intranasally into foals, specifically free from EHV-1 and EHV-4. Clinical signs, including rectal temperature, were similar for both viruses. In addition, nasal shedding of virus was observed over a 1- to 2-week period postinfection, and viremia was established with both Ab4 and Ab4p. Isolation of virus from one foal following intravenous administration of steroids indicates that Ab4p can establish latency and undergo reactivation. Finally, retinal lesions were observed and these were similar to those seen with Ab4. In conclusion, several pathogenic characteristics of Ab4 are retained in the plaque-purified clone, Ab4p.

Animals↗
PubMed2004

Identification and characterization of NleA, a non-LEE-encoded type III translocated virulence factor of enterohaemorrhagic Escherichia coli O157:H7.

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 uses a specialized protein translocation apparatus, the type III secretion system (TTSS), to deliver bacterial effector proteins into host cells. These effectors interfere with host cytoskeletal pathways and signalling cascades to facilitate bacterial survival and replication and promote disease. The genes encoding the TTSS and all known type III secreted effectors in EHEC are localized in a single pathogenicity island on the bacterial chromosome known as the locus for enterocyte effacement (LEE). In this study, we performed a proteomic analysis of proteins secreted by the LEE-encoded TTSS of EHEC. In addition to known LEE-encoded type III secreted proteins, such as EspA, EspB and Tir, a novel protein, NleA (non-LEE-encoded effector A), was identified. NleA is encoded in a prophage-associated pathogenicity island within the EHEC genome, distinct from the LEE. The LEE-encoded TTSS directs translocation of NleA into host cells, where it localizes to the Golgi apparatus. In a panel of strains examined by Southern blot and database analyses, nleA was found to be present in all other LEE-containing pathogens examined, including enteropathogenic E. coli and Citrobacter rodentium, and was absent from non-pathogenic strains of E. coli and non-LEE-containing pathogens. NleA was determined to play a key role in virulence of C. rodentium in a mouse infection model.

Amino Acid Sequence↗