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Results for “Pathogen genomics”

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PubMed2005

Small RNA genes expressed from Staphylococcus aureus genomic and pathogenicity islands with specific expression among pathogenic strains.

Small RNA (sRNA) genes are expressed in all organisms, primarily as regulators of translation and message stability. We have developed comparative genomic approaches to identify sRNAs that are expressed by Staphylococcus aureus, the most common cause of hospital-acquired infections. This study represents an in-depth analysis of the RNome of a Gram-positive bacterium. A set of sRNAs candidates were identified in silico within intergenic regions, and their expression levels were monitored by using microarrays and confirmed by Northern blot hybridizations. Two sRNAs were also detected directly from purification and RNA sequence determination. In total, at least 12 sRNAs are expressed from the S. aureus genome, five from the core genome and seven from pathogenicity islands that confer virulence and antibiotic resistance. Three sRNAs are present in multiple (two to five) copies. For the sRNAs that are conserved throughout the bacterial phylogeny, their secondary structures were inferred by phylogenetic comparative methods. In vitro binding assays indicate that one sRNA encoded within a pathogenicity island is a trans-encoded antisense RNA regulating the expression of target genes at the posttranscriptional level. Some of these RNAs show large variations of expression among pathogenic strains, suggesting that they are involved in the regulation of staphylococcal virulence.

Base Pairing↗
PubMed2002

Functional and comparative genomics of pathogenic bacteria.

Microarray expression profiling and the development of data-mining tools and new statistical instruments affords an unprecedented opportunity for the genome-scale study of bacterial pathogenicity. Expression profiles obtained from bacteria grown in media simulating host microenvironments yield a portrait of interacting metabolic pathways and multistage developmental programs and disclose regulatory networks. The analysis of closely related strains and species by microarray-based comparative genomics provides a measure of genetic variability within natural populations and identifies crucial differences between pathogen and commensal. In the near future, the combined use of bacterial and host microarrays to study the same infected tissue will reveal the host-pathogen dialogue in a gene-by-gene and site- and time-specific manner. This review discusses the use of microarray-based expression profiling to identify genes of pathogenic bacteria that are differentially regulated in response to host-specific signals. Additionally, the review describes the application of microarray methods to disclose differences in gene content between taxonomically related strains that vary with respect to pathogenic phenotype.

Animals↗
PubMed1996

Characterization of pathogenic fungi genomes using pulsed field gel electrophoresis.

Pulsed field gel electrophoresis (PFGE) has been firstly introduced in characterization of the pathogenic fungi Penicillium marneffei and Exophiala dermatitidis genomes. The numbers and sizes of their chromosomes have been detected. Polymorphism was identified on the smallest chromosome of E. dermatitidis. The result shows that PFGE for characterization of large molecular DNA pathogenic fungi is very suitable, it is more simple and more efficacy. The result also shows the diversity of pathogenic fungi is relative common even in rare occurred pathogenic fungi such as E. dermatitidis.

DNA, Fungal↗
PubMed2002

Functional genomics of pathogenic bacteria.

Microbial diseases remain the commonest cause of global mortality and morbidity. Automated-DNA sequencing has revolutionized the investigation of pathogenic microbes by making the immense fund of information contained in their genomes available at reasonable cost. The challenge is how this information can be used to increase current understanding of the biology of commensal and virulence behaviour of pathogens with particular emphasis on in vivo function and novel approaches to prevention. One example of the application of whole-genome-sequence information is afforded by investigations of the pathogenic role of Haemophilus influenzae lipopolysaccharide and its candidacy as a vaccine.

Gene Expression Regulation, Bacterial↗
PubMed2000

Microbial genome analysis: insights into virulence, host adaptation and evolution.

Genome analysis of microbial pathogens has provided unique insights into their virulence, host adaptation and evolution. Common themes have emerged, including lateral gene transfer among enteric pathogens, genome decay among obligate intracellular pathogens and antigenic variation among mucosal pathogens. The advent of post-genomic approaches and the sequencing of the human genome will enable scientists to investigate the complex and dynamic interplay between host and pathogen. This wealth of information will catalyse the development of new intervention strategies to reduce the burden of microbial-related disease.

Adaptation, Physiological↗
PubMed2026

Advancing One Health genomics in Africa: opportunities and challenges for outbreak and antimicrobial resistance control.

SUMMARYAfrica's ongoing struggles with emerging epidemics and antimicrobial resistance (AMR) underscore the urgency of integrating pathogen genomics and surveillance systems into the continent's One Health strategy, particularly given the existing limitations in preparedness and technological resources. This review brings together current evidence on the growth of sequencing infrastructure, the development of regional genomic hubs, and the establishment of governance frameworks, while identifying critical challenges in data integration, bioinformatics capacity, and sustainable financing. Special focus is placed on the lack of African-based genomic data, with our analysis showing that only 1.82% of the global total is available. Case studies illustrate the immense potential and importance of pathogen genomics, giving policymakers a tangible sense of its impact. These examples demonstrate how genomic technologies integrated with artificial intelligence (AI) are transforming outbreak response, AMR surveillance, and stewardship programs by enabling early detection of zoonotic threats, mapping transmission pathways, and guiding vaccine development. However, to fully realize this scientific intel, it is essential to embed One Health pathogen surveillance within strong policy and system frameworks to ensure the translation of technical progress into lasting institutional capacity and sustainable impact. Long-term implementation depends on coordinated investment and advocacy across four interdependent pillars: data architecture, governance and sovereignty, human capital, and technical capacity.

Humans↗
PubMed1989

Comparison of the genomes of pathogenic treponemes of human and animal origin.

The aim of this study was to compare the genomes of two strains of intestinal treponemes, which were isolated from patients suffering from intestinal disorders, with that of Treponema hyodysenteriae, the known etiological agent of swine dysentery (bloody scours). The guanine-plus-cytosine contents of the three DNAs were found to be 28.5 to 30.0%. DNA-DNA hybridization in liquid phase indicated a high degree of homology (56 to 95%) among the human strains and with T. hyodysenteriae. One of the human strains in particular displayed a very high homology (91 to 95%) with T. hyodysenteriae. The overall conclusion is that treponemal strains pathogenic for humans and animals are clustered within the same species (we propose T. hyodysenteriae), which suggests the possibility of exchange of pathogenic microorganisms between domestic animals and humans.

Animals↗
PubMed2004

Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion.

Comparative genomics demonstrated that the chromosomes from bacteria and their viruses (bacteriophages) are coevolving. This process is most evident for bacterial pathogens where the majority contain prophages or phage remnants integrated into the bacterial DNA. Many prophages from bacterial pathogens encode virulence factors. Two situations can be distinguished: Vibrio cholerae, Shiga toxin-producing Escherichia coli, Corynebacterium diphtheriae, and Clostridium botulinum depend on a specific prophage-encoded toxin for causing a specific disease, whereas Staphylococcus aureus, Streptococcus pyogenes, and Salmonella enterica serovar Typhimurium harbor a multitude of prophages and each phage-encoded virulence or fitness factor makes an incremental contribution to the fitness of the lysogen. These prophages behave like "swarms" of related prophages. Prophage diversification seems to be fueled by the frequent transfer of phage material by recombination with superinfecting phages, resident prophages, or occasional acquisition of other mobile DNA elements or bacterial chromosomal genes. Prophages also contribute to the diversification of the bacterial genome architecture. In many cases, they actually represent a large fraction of the strain-specific DNA sequences. In addition, they can serve as anchoring points for genome inversions. The current review presents the available genomics and biological data on prophages from bacterial pathogens in an evolutionary framework.

Bacteria↗
PubMed2000

Chemical ligands, genomics and drug discovery.

The sequencing of the human genome and numerous pathogen genomes has resulted in an explosion of potential drug targets. These targets represent both an unprecedented opportunity and a technological challenge for the pharmaceutical industry. A new strategy is required to initiate small-molecule drug discovery with sets of incompletely characterized, disease-associated proteins. One such strategy is the early application of combinatorial chemistry and other technologies to the discovery of bioactive small-molecule ligands that act on candidate drug targets. Therapeutically active ligands serve to concurrently validate a target and provide lead structures for downstream drug development, thereby accelerating the drug discovery process.

Journal Article↗
PubMed2003

Virtual screening on natural products for discovering active compounds and target information.

Natural products, containing inherently large-scale structural diversity than synthetic compounds, have been the major resources of bioactive agents and will continually play as protagonists for discovering new drugs. However, how to access this diverse chemical space efficiently and effectively is an exciting challenge for medicinal chemists and pharmacologists. While virtual screening, which has shown a great promise in drug discovery, will play an important role in digging out lead (active) compounds from natural products. This review focuses on the strategy of virtual screening based on molecular docking and, with successful examples from our laboratory, illustrates the efficiency of virtual screening in discovering active compounds from natural products. On the other hand, the sequencing of the human genome and numerous pathogen genomes has resulted in an unprecedented opportunity for discovering potential new drug targets. Chemogenomics has appeared as a new technology to initiate target discovery by using active compounds as probes to characterize proteome functions. Natural products are the ideal probes for such research. Binding affinity fingerprint is a powerful chemogenomic descriptor to characterize both small molecules and pharmacologically relevant proteins. Therefore, this review also discusses binding affinity fingerprint strategy for identifying target information from the genomic data by using natural products as the probes.

Biological Products↗
PubMed2004

Revisiting the pestilence of Helicobacter pylori: insights into geographical genomics and pathogen evolution.

Helicobacter pylori causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. It is believed that H. pylori infects over 50% of the worlds' population. However, only a small subset of infected people experience H. pylori-associated illnesses. Associations with disease-specific factors remain enigmatic. The contribution of comparative genomics to our understanding of the genome organisation and diversity of H. pylori is exemplified herein. The discovery of the cag pathogenicity island has revolutionised our understanding of the molecular pathogenesis of gastroduodenal ulcers. Another type IV secretion system, the comB gene cluster, provides a novel transformation system. Identification of this cluster has boosted our perception of horizontal gene transfer and gene mosaicism in H. pylori as a result of natural competence. Recent discovery of a third type IV secretion system called tfs3 encoding cluster in the so called plasticity zone of the H. pylori has gained significant attention, although its role is not clear. Study of the evolution of polymorphisms and sequence variation in H. pylori populations on a global basis is contributing to understanding of the history of human population migration and co-evolution of this pathogen with its human host. Possible symbiotic relationships were debated since the discovery of this pathogen. The debate has been further intensified as recent studies have posed the intriguing possibility that H. pylori infection may be advantageous in some humans. This analogy is based on increased incidence of diseases like gastro-oesophageal reflux disease (GERD), Barrett's oesophagus and adenocarcinoma of the oesophagus following H. pylori eradication in some patients.

Disease Transmission, Infectious↗
PubMed2006

A novel approach to characterise pathogen candidate genetic polymorphisms involved in clinical outcome.

Understanding the key factors influencing the clinical outcome of an infection is crucial for early diagnosis and optimised treatment. Despite widespread recognition of the importance of the genetics composition of pathogens, most efforts so far have focused on characterising disease and susceptibility genes in humans. Here, we propose a new flexible and powerful methodological framework to detect candidate genetic polymorphisms influencing clinical outcome from pathogen genomes. The rationale is to use well-supported clades in a phylogeny as statistical predictors for clinical outcomes rather than the individual polymorphisms themselves. This greatly increases the statistical power to detect candidate polymorphisms when analysing a large number of variable sites. In a second step, the candidate polymorphisms are recovered by characterising the polymorphisms that most strongly support the clades predicting the clinical outcome. The modelling approach further allows including host factors and testing for possible interactions between factors. We illustrate the approach by an application on a dataset of hepatitis B polymerase genes. The statistical model retains age at infection as well as six candidate polymorphisms as predictors for clinical outcome (acute, chronic and fulminant). The method is straightforward to apply and computationally effective. While the approach is focused on detecting candidate polymorphisms from pathogen genomes, the method might be more broadly applied for characterising the link between genotype and phenotype while statistically controlling for environmental factors.

Hepatitis B virus↗
PubMed2001

Whole genome plasticity in pathogenic bacteria.

The exploitation of bacterial genome sequences has so far provided a wealth of new general information about the genetic diversity of bacteria, such as that of many pathogens. Comparative genomics uncovered many genome variations in closely related bacteria and revealed basic principles involved in bacterial diversification, improving our knowledge of the evolution of bacterial pathogens. A correlation between metabolic versatility and genome size has become evident. The degenerated life styles of obligate intracellular pathogens correlate with significantly reduced genome sizes, a phenomenon that has been termed "evolution by reduction". These mechanisms can permanently alter bacterial genotypes and result in adaptation to their environment by genome optimization. In this review, we summarize the recent results of genome-wide approaches to studying the genetic diversity of pathogenic bacteria that indicate that the acquisition of DNA and the loss of genetic information are two important mechanisms that contribute to strain-specific differences in genome content.

Bacteria↗
PubMed2000

Genomic and pathogenic studies on a glycoprotein E variant field isolate of bovine herpesvirus 1.

Glycoprotein E-negative (gE-) laboratory strains of bovine herpesvirus 1 (BHV-1) were recently introduced as novel marker vaccines, allowing serological discrimination between vaccinated and naturally infected animals on the basis of lack or presence of antibodies against gE epitopes. The applicability pf this approach is based on the genetic stability of the gE. However, mutant field variants of BHV-1 with a variable response in anti-gE ELISA have been isolated. The molecular characterization of a gE variant field isolate (Salwa strain) is presented here. By comparing the gE nucleotide and amino acid sequences of the Salwa strain with those of the wild strain Jura, ten mutated bases were found in the gE strain of Salwa, six of which alter the amino acid sequence, leading to changes in five amino acids. Both strains caused respiratory disease in experimentally infected calves, but Salwa generated slightly milder signs. Both viruses were excreted in nasal and ocular discharges, and were reactivated by dexamethasone treatment. In conclusion, the rather close similarities observed in the gE gene structure and pathogenicity features of the gE mutant and of the wild strain of BHV-1 confirm the genetic stability of gE. The findings indicate that the Salwa isolate is virulent, but less virulent than wild strains. Our data support the use of gE-negative marker vaccines in eradication programmes.

Amino Acid Sequence↗