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Results for “host:pathogen interactions”

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PubMed1999

Regulation and temporal expression patterns of Vibrio cholerae virulence genes during infection.

The temporal expression patterns of the critical Vibrio cholerae virulence genes, tcpA and ctxA, were determined during infection using a recombinase reporter. TcpA was induced biphasically in two temporally and spatially separable events in the small intestine, whereas ctxA was induced monophasically only after, and remarkably, dependent upon, tcpA expression; however, this dependence was not observed during in vitro growth. The requirements of the virulence regulators, ToxR, TcpP, and ToxT, for expression of tcpA and ctxA were determined and were found to differ significantly during infection versus during growth in vitro. These results illustrate the importance of examining virulence gene expression in the context of bona fide host-pathogen interactions.

Animals↗

PubMed2000

Identification of mariner-like elements from the root-knot nematode Meloidogyne spp.

The Meloidogyne species are agriculturally important pests widespread in the world. These polyphagous endoparasitic nematodes possess an astonishing ability to bypass the plant resistance genes in few generations. However, the genes and mechanisms involved in this molecular determinism are not yet known. Except cytogenetic and cytotaxonomic studies, few data are available concerning their genome. There is therefore an important need of molecular tools for genetic investigation of their virulence character and other aspects of host-pathogen interactions. In that respect, the presence of mariner-like-elements (MLEs) was assessed in these endoparasitic nematodes by a polymerase chain reaction (PCR) assay using degenerate primers designed from two conserved regions of the mariner transposase open reading frame (ORF). Four Meloidogyne species of the five tested revealed the presence of MLEs in their genome. Southern blot analysis indicated that sequences hybridizing to the mariner transposase-like PCR clones occur at a moderate to low copy number in the different Meloidogyne spp. genomes. The phylogenetic analysis show that the Meloidogyne MLEs may form new subfamilies of mariner. Moreover, five PCR clones were shown to possess a continuous ORF suggesting the presence of putative transposase-like coding regions.

Amino Acid Sequence↗

PubMed2000

Genes that fight infection: what the Drosophila genome says about animal immunity.

From deciphering the principles of heredity to identifying the genes that control development, the fruit fly Drosophila melanogaster is being used to deconstruct an increasing number of biological processes. Genetic studies of Drosophila responses to microbial infection have identified regulators of innate immunity that are functionally conserved in mammals. These recent findings highlight the ancient origins of animal immune responses and demonstrate the potential of Drosophila for dissecting host-pathogen interactions. The sequencing of the Drosophila genome both enhances genetic approaches and provides new clues for the identification of key components of innate immunity. This article summarizes how information gained from genomic analysis contributes to our understanding of how animals cope with infectious disease.

Adaptation, Physiological↗

PubMed1997

HLA class I and class II allele and haplotype distribution in the Venezuelan population.

Population studies represent an integral part, and a necessary link in a complex chain of host-pathogen interactions, disease pathogenesis, and major histocompatibility complex polymorphism. HLA class I and class II allele and haplotype distributions among Venezuelan mestizos were determined. Genes of Mongoloid, Negroid, and Caucasoid origin have created a distinctive human leukocyte antigen (HLA) genetic profile in this hybrid mestizo population that will influence HLA and disease association studies. The predominant HLA-B DQA1 DQB1 DRB1 haplotype is HLA-B44 DQA1*0201 DQB1*0201 DRB1*0701 (5.3%). It is noteworthy that the HLA-A3 B7 DR2 and the HLA-A1 B8 DR3 linkage groups, which are part of conserved or ancestral haplotypes, the last one associated with a wide range of autoimmune diseases and immune abnormalities in apparently healthy subjects, show low incidence among Venezuelan mestizos. This fact may be useful for future HLA and disease association studies and for localization of genes involved in immune regulation associated with these haplotypes.

Adult↗

PubMed2001

Gene expression microarrays: a 21st century tool for directed vaccine design.

DNA microarray technology is a new and powerful tool that allows the simultaneous analysis of a large number of nucleic acid hybridization experiments in a rapid and efficient fashion. The development of the DNA microarray chip has been driven by modern techniques of microelectronic fabrication, miniaturization and integration to produce what is referred to as "laboratory-on-chip" devices. The application of DNA chip technology includes the comprehensive analysis of multiple gene mutations and expressed sequences with regard to newer drug designs, host-pathogen interactions and the design of new vaccines. An advantage of microarray technology is that it can assist researchers to better define and understand the expression profile of a given genotype associated with disease, adverse effects from exposure to certain stimuli, or the ability to understand or predict immune responses to specific antigens. This paper briefly reviews DNA microarray technology and its implications with special reference to vaccine design. The technical aspects comprising array manufacturing and design, array hybridization, formatting, scanning and data handling are also briefly discussed.

Animals↗

PubMed2003

Novel human vaccine strategies and the 5th Framework Programme: pushing the envelope.

Mucosal vaccines could result in a great scientific and practical achievement. More than three decades of research in experimental models have shown promising results in stimulating mucosal immune responses, thus, it was expected that within a short time mucosal vaccines for human use could be achieved. Indeed this is not being the case. In the last few years, the most important oral vaccine, the anti-polio developed by Sabin in the fifties, has been progressively abandoned in developed countries to avoid the few cases of disease caused by the vaccine. Furthermore, two recently developed mucosal vaccines for human use against rotavirus diarrhoea and influenza were withdrawn after a short period in the market because of adverse reactions among the vaccinees. This controversial situation has created a difficult future for research on mucosal vaccine at the industrial level. A great help and encouragement for believers in mucosal vaccines has been given by the EU Commission through the 5th Framework Programme (5FP). At the end of the first projects of the 5FP, it is quite clear that mucosal vaccines are experiencing a real renaissance. The Euroconference/Workshop "Novel Strategies of Mucosal Immunisation through Exploitation of Mechanisms of Innate Immunity in Pathogen-Host Interaction", organised under the sponsorship of the EU Commission and reported in this special issue of Vaccine, witnesses a very creative moment of European groups involved in mucosal immunology. This conclusive paper of the issue is intended to describe a positive experience of some European scientists that have been working together in organised fashion within two EU projects. The first, defined by the acronym MUCIMM, was aimed to pave the way to tackle mucosal vaccines with different approaches, mainly that of new delivery systems and adjuvants, that of dissecting the fine mechanisms of basic mucosal responses and that of obtaining meaningful assays to measure human immune responses to mucosal vaccines. The second, the MUCADJ project, was aimed to prove that an intranasally delivered influenza vaccine induces protective levels of immunity in human adult volunteers. The results obtained demonstrate that mucosal vaccines for humans are feasible. It is interesting to note how this model of making biomedical research is flourishing, becoming an example for work organisation. At the same time it is important to underline some of the limits of this cooperative approach and it is also mandatory to spend a word of consciousness regarding the impact that the new European regulations could exert on mucosal vaccines, particularly for those based on live delivery systems. In a world where the damages caused by syringe needles are still largely visible, mucosal vaccines could represent an extremely important tool to fight infections, particularly in the large population of the most impoverished. The EU Commission will still encourage and support mucosal vaccines in the 6FP. The scientific community must decide in which direction has to proceed to avoid regulatory problems that could halt a promising tool to improve human health. The envelope has been pushed, the trip begins.

Europe↗

PubMed2001

Characterization and comparative analysis of the EGLN gene family.

Rat Sm-20 is a homologue of the Caenorhabditis elegans gene egl-9 and has been implicated in the regulation of growth, differentiation and apoptosis in muscle and nerve cells. Null mutants in egl-9 result in a complete tolerance to an otherwise lethal toxin produced by Pseudomonas aeruginosa. This study describes the conserved Egl-Nine (EGLN) gene family of which rat SM-20 and C. elegans Egl-9 are members and characterizes the mouse and human homologues. Each of the human genes (EGLN1, EGLN2 and EGLN3) are of a conserved genomic structure consisting of five coding exons. Phylogenetic analysis and domain organization show that EGLN1 represents the ancestral form of the gene family and that EGLN3 is the human orthologue of rat Sm-20. The previously observed mitochondrial targeting of rat SM-20 is unlikely to be a general feature of the protein family and may be a feature specific to rats. An EGLN gene is unexpectedly found in the genome of P. aeruginosa, a bacterium known to produce a toxin that acts through the Egl-9 protein. The pathogenic bacterium Vibrio cholerae is also shown to have an EGLN gene suggesting that it is an important pathogenicity factor. These results provide new insights into host-pathogen interactions and a basis for further functional characterization of the gene family and resolve discrepancies in annotation between gene family members.

Amino Acid Sequence↗

PubMed1998

Characterization of mechanisms involved in uptake of Streptococcus dysgalactiae by bovine mammary epithelial cells.

Bovine mammary epithelial cells were pretreated with inhibitors of protein kinase activity, actin polymerization and receptor-mediated endocytosis. In addition, mammary epithelial cells and Streptococcus dysgalactiae were pretreated with inhibitors of protein synthesis. Results showed that activity of tyrosine protein kinases, intact microfilaments and de novo eukaryotic protein synthesis was required for uptake of S. dysgalactiae by bovine mammary epithelial cells; a process that appeared to occur via receptor-mediated endocytosis. In contrast, de novo bacterial protein synthesis was not required for uptake of S. dysgalactiae by MAC-T cells. This study provides insight into bacterial and cellular mechanisms involved in early host-pathogen interactions, putting into perspective the role of mammary epithelial cells in the development and establishment of intramammary infections by S. dysgalactiae.

Actins↗

PubMed1998

Innate immunity, cytokines, and pulmonary host defense.

Effective host defense against bacterial infection is dependent on the activation and recruitment of phagocytic cells. The initiation, maintenance, and resolution of this inflammatory response in the setting of bacterial pneumonia is dependent on the expression of cytokines. As the complexities of the host-pathogen interaction are further dissected and unraveled, immunologic manipulation of cytokine expression will likely become an important adjuvant therapy in the treatment of serious lung infections.

Animals↗

PubMed2002

Disease consequences of pathogen adaptation.

Experimental evolution studies demonstrate that pathogens evolve rapidly, have a large capacity for increased virulence and cause disease in many different ways. A large proportion of genetic diversity for host susceptibility to infectious, autoimmune and 'genetic' diseases, and to cancer, is probably caused by pathogens and/or host counteradaptations. Recent advances in diverse fields support this claim and suggest many underused approaches for identifying and experimentally dissecting the complicated host-pathogen interactions that often lead to disease.

Adaptation, Physiological↗

PubMed2000

Salmonella typhimurium proliferates and establishes a persistent infection in the intestine of Caenorhabditis elegans.

Genetic analysis of host-pathogen interactions has been hampered by the lack of genetically tractable models of such interactions. We showed previously that the human opportunistic pathogen Pseudomonas aeruginosa kills Caenorhabditis elegans, that P. aeruginosa and C. elegans genes can be identified that affect this killing, and that most of these P. aeruginosa genes are also important for mammalian pathogenesis. Here, we show that Salmonella typhimurium as well as other Salmonella enterica serovars including S. enteritidis and S. dublin can also kill C. elegans. When C. elegans is placed on a lawn of S. typhimurium, the bacteria accumulate in the lumen of the worm intestine and the nematodes die over the course of several days. This killing requires contact with live bacterial cells. The worms die with similar kinetics when placed on a lawn of S. typhimurium for a relatively short time (3-5 hours) before transfer to a lawn of E. coli. After the transfer to E. coli, a high titer of S. typhimurium persists in the C. elegans intestinal lumen for the rest of the worms' life. Furthermore, feeding for 5 hours on a 1:1000 mixture of S. typhimurium and E. coli followed by transfer to 100% E. coli, also led to death after several days. This killing correlated with an increase in the titer of S. typhimurium in the C. elegans lumen, which reached 10,000 bacteria per worm. These data indicate that, in contrast to P. aeruginosa, a small inoculum of S. typhimurium can proliferate in the C. elegans intestine and establish a persistent infection. S. typhimurium mutated in the PhoP/PhoQ signal transduction system caused significantly less killing of C. elegans.

Animals↗

PubMed2003

The basis of persistent bacterial infections.

Selected bacterial pathogens, such as Helicobacter pylori and Mycobacterium tuberculosis, establish persistent infections in mammalian hosts despite activating inflammatory and antimicrobial responses. The strategies used to overcome host defense responses vary with the anatomical location of the infection but often rely on deliberate manipulations of the host cell responses. Phylogenetically unrelated bacteria can share similar strategies for the establishment of persistence and, in selected examples, one even can define homologous "persistence" genes. Such observations suggest that persistent infection is a specific phase in infection pathogenesis rather than a fortuitous imbalance in the host-pathogen interaction.

Animals↗

PubMed2002

Surface proteins and the pathogenic potential of Listeria monocytogenes.

On the basis of the recently determined genome sequence of Listeria monocytogenes, we performed a global analysis of the surface-protein-encoding genes. Only proteins displaying a signal peptide were taken into account. Forty-one genes encoding LPXTG proteins, including the previously known internalin gene family, were detected. Several genes encoding proteins that, like InlB and Ami, possess GW modules that attach them to lipoteichoic acids were also identified. Additionally, the completed genome sequence revealed genes encoding proteins potentially anchored in the cell membrane by a hydrophobic tail as well as genes encoding P60-like proteins and lipoproteins. We describe these families and discuss their putative implications for host-pathogen interactions.

Amino Acid Motifs↗

PubMed2003

A new turn in Rho GTPase activation by Escherichia coli cytotoxic necrotizing factors.

Various bacterial protein toxins and effectors target Rho GTPases, which are eukaryotic regulators of signal transduction pathways. Many toxins inactivate these GTPases but some, such as the cytotoxic necrotizing factors (CNFs) from Escherichia coli, activate them by deamidation. Recent studies have provided exciting new clues to the functional consequences of the activation of Rho GTPases by CNFs and its effect on the host-pathogen interaction.

Bacterial Infections↗

PubMed1999

The cytolethal distending toxin family.

Cytolethal distending toxins are produced by a small but diverse group of bacterial pathogens. This newly discovered toxin family can cause a variety of mammalian cells to become irreversibly blocked in the G2 phase of the cell cycle. How this novel effect is accomplished is unknown but the study of these fascinating toxins promises to reveal new methods of host-pathogen interaction.

Aggregatibacter actinomycetemcomitans↗

PubMed1999

Probing the microenvironment of intracellular bacterial pathogens.

The identification of bacterial genes regulated in response to the intracellular environment is crucial to the understanding of host-pathogen interactions. Several techniques have been developed to identify and characterize bacterial genes that are induced during the intracellular infection and, potentially, may play a role in pathogenesis. This review discusses the strategies that have been utilized to examine differential gene expression by bacterial pathogens during the intracellular infection. Furthermore, a number of the differentially expressed genes are described.

Animals↗

PubMed2005

The rational design of vaccines.

This review provides an insight into the various opportunities for vaccine intervention, analysis of strategies for vaccine development, vaccine ability to modulate immune responses and resultant rational vaccine design. In addition, wider aspects are considered, such as biotechnological advances, advances in immunological understanding and host-pathogen interactions. The key question addressed here is, with all our research and understanding, have we reached a new echelon in vaccine development, that of rational design?

Drug Delivery Systems↗

PubMed2000

Prospects for understanding avirulence gene function.

Avirulence genes are originally defined by their negative impact on the ability of a pathogen to infect their host plant. Many avirulence genes are now known to represent a subset of virulence factors involved in the mediation of the host-pathogen interaction. Characterization of avirulence genes has revealed that they encode an amazing assortment of proteins and belong to several gene families. Although the biochemical functions of the avirulence gene products are unknown, studies are beginning to reveal the features and interesting relationships between the avirulence and virulence activities of the proteins. Identification of critical virulence factors and elucidation of their functions promises to provide insight into plant defense mechanisms, and new and improved strategies for the control of plant disease.

Amino Acid Sequence↗