SEARCH · PubMed Health

Results for “host:pathogen interactions”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 721 records · Page 40Linked to original sources

PubMed2005

Inactivation of polyketide synthase and related genes results in the loss of complex lipids in Mycobacterium tuberculosis H37Rv.

AIMS: Phthiocerol dimycocerosate (PDIM) waxes and other lipids are necessary for successful Mycobacterium tuberculosis infection, although the exact role of PDIM in host-pathogen interactions remains unclear. In this study, we investigated the contribution of tesA, drrB, pks6 and pks11 genes in complex lipid biosynthesis in M. tuberculosis. METHODS AND RESULTS: Four mutants were selected from M. tuberculosis H37Rv transposon mutant library. The transposon insertion sites were confirmed to be within the M. tuberculosis open reading frames for tesA (a probable thioesterase), drrB (predicted ABC transporter), pks11 (putative chalcone synthase) and pks6 (polyketide synthase). The first three of these transposon mutants were unable to generate PDIM and the fourth lacked novel polar lipids. CONCLUSIONS: Mycobacterium tuberculosis can be cultivated in vitro without the involvement of certain lipid synthesis genes, which may be necessary for in vivo pathogenicity. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of transposon mutants is a new functional genomic approach for the eventual definition of the mycobacterial 'lipidome'.

ATP-Binding Cassette Transporters↗

PubMed2004

Regulation of aging and innate immunity in C. elegans.

The free-living soil nematode Caenorhabditis elegans is a versatile model for the study of the genetic regulation of aging and of host-pathogen interactions. Many genes affecting multiple processes, such as neuroendocrine signalling, nutritional sensing and mitochondrial functions, have been shown to play important roles in determining the lifespan of C. elegans. The DAF-2-mediated insulin signalling pathway is the major pathway that regulates aging in this nematode and this role appears universal; neuroendrocrine signalling also affects aging in Drosophila and mice. Recent studies have shown that the innate immune function in C. elegans is modulated by signalling from the TGF-beta-like, the p38 MAPK and the DAF-2 insulin pathways. The requirement for the DAF-2 pathway in modulating aging and immunity suggests that these processes may be linked at the molecular level. It is well known that as humans age, immunosenescence occurs in which there is a general degradation of immune efficiency. However, the molecular mechanisms involved in this process remain unclear. In this review, we discuss the molecular mechanisms that modulate aging and immune response and attempt to suggest molecular links between these two processes.

Aging↗

PubMed2005

Visualization of Helicobacter species within the murine cecal mucosa using specific fluorescence in situ hybridization.

BACKGROUND: Members of the genus Helicobacter have been associated with colitis development in a number of immunodeficient animal models. While it is known that these organisms can initiate colitis development, the location and spatial distribution of these bacteria within the intestinal tract is currently unknown. In this study, we developed and optimized fluorescence in situ hybridization (FISH) probes specifically for Helicobacter species. MATERIALS AND METHODS: Based on 16S-RNA gene alignments, two probes specific for the entire family Helicobacteraceae and two probes specific for Helicobacter ganmani and Helicobacter hepaticus were designed. Evaluation of these probes was determined using ATCC reference strains and cecum samples from ten IL-10 knockout mice. The presence of Helicobacter species was determined using FISH and verified using PCR-DGGE and microscopic examination of silver stained sections. RESULTS: Analysis of the ATCC reference strains revealed that the probes HEL274/HEL717 were specific for the family Helicobacteraceae, while HEP642 was specific for H. hepaticus and GAN1237 for H. ganmani. Using these probes, a pattern of spatial localization of the two different Helicobacter species was observed in the cecum tissues of IL-10 knockout mice. This consistently showed that H. ganmani was localized to the lower regions and H. hepaticus to the mid-upper regions of the crypts. CONCLUSION: We have developed FISH probes specific for the family Helicobacteraceae as well as two individual Helicobacter species. This study will allow the future use of the FISH to better understand host-pathogen interactions in vitro.

Animals↗

PubMed2006

Tumour necrosis factor alpha mediated apoptosis in murine macrophages by Salmonella enterica serovar Typhi under oxidative stress.

Invasive Salmonella has been reported to induce apoptosis of macrophages as part of its infection process, which may allow it to avoid detection by the innate immune system. However, the induction of apoptosis under the different host environments remains to be examined, including the oxidative stress experienced by pathogens in the macrophage milieu. To simulate in vivo oxidative conditions, Salmonella enterica serovar Typhi was grown in the presence of hydrogen peroxide and its ability to induce apoptosis of murine macrophages was assessed. Analysis of data revealed that oxidative stressed S. Typhi caused apoptotic cell death in 51% of macrophages, whereas S. Typhi grown under normal conditions accounted for apoptotic cell death in only 32% of macrophages. A significant increase in the levels of oxidants and decrease in the antioxidant was also observed which correlated with the increased generation of tumour necrosis factor alpha, interleukin-1alpha and interleukin-6. These results suggest that tumour necrosis factor alpha in conjunction with other cytokines may induce apoptotic cell death through the up-regulation of lipid peroxidation and down-regulation of superoxide dismutase. This finding may help us to understand better the host-pathogen interactions and may be of clinical importance in the development of preventive intervention against infection.

Acridine Orange↗

PubMed1999

Green fluorescent protein as a detection marker for Coxiella burnetii transformation.

The molecular biological study of the obligate intracellular bacterium Coxiella burnetii is hampered because of the lack of an efficient DNA transformation system. We used expression of the green fluorescent protein (GFP) in addition to ampicillin resistance as a selection marker for detection of transformed C. burnetii cells. Fluorescent microscopy studies revealed that transformed C. burnetii cells can be detected easily inside the host cell line. A high level of GFP expression was reached with the strong Escherichia coli trc (trp/lac) promoter. The use of GFP not only provides a convenient marker for transformation of C. burnetii, but also allows detection of this obligate intracellular pathogen inside host eukaryotic cells. Possible applications for GFP in the study of host-pathogen interactions are discussed.

Ampicillin Resistance↗

PubMed2000

Urease of Corynebacterium glutamicum: organization of corresponding genes and investigation of activity.

The Corynebacterium glutamicum genes encoding urease were isolated and sequenced. While ureA, ureB and ureC are encoding structural subunits of urease, ureE, ureF, ureG and ureD are encoding accessory proteins. As deduced from DNA sequence analyses, the ure genes are transcriptionally coupled, this was proven by RT-PCR at least for ureABC. Gene disruption experiments revealed that both structural (UreC) and accessory proteins (UreD) are indispensable for urease activity and growth on urea. Urease activity was determined in different Corynebacterium species after growth in various media. While the regulation patterns observed revealed species-specific differences, in general urease activity is induced upon nitrogen starvation. As in mycobacteria, in corynebacteria urease activity was highest in a pathogenic species and might also play a role in host-pathogen interaction.

Bacterial Proteins↗

PubMed2002

Molecular analysis of ancient microbial infections.

The detection of ancient microbial DNA offers a new approach for the study of infectious diseases, their occurrence, frequency and host-pathogen interaction in historic times and populations. Moreover, data obtained from skeletal and mummified tissue may represent an important completion of contemporary phylogenetic analyses of pathogens. In the last few years, a variety of bacterial, protozoal and viral infections have been detected in ancient tissue samples by amplification and characterization of specific DNA fragments. This holds particularly true for the identification of the Mycobacterium tuberculosis complex, which seems to be more robust than other microbes due to its waxy, hydrophobic and lipid-rich cell wall. These observations provided useful information about the occurrence, but also the frequency of tuberculosis in former populations. Moreover, these studies suggest new evolutionary models and indicate the route of transmission between human and animals. Until now, other pathogens, such as Mycobacterium leprae, Yersinia pestis, Plasmodium falciparum and others, have occasionally been identified - mostly in single case studies or small sample sizes - as well, although much less information is available on these pathogens in ancient settings. The main reason therefore seems to be the degradation and modification of ancient DNA by progressive oxidative damage. Furthermore, the constant risk of contamination by recent DNA forces to take time and cost effective measures and renders the analysis of ancient microbes difficult. Nevertheless, the study of microbial ancient DNA significantly contributes to the understanding of transmission and spread of infectious diseases, and potentially to the evolution and phylogenetic pathways of pathogens.

Animals↗

PubMed2006

An EST library from Puccinia graminis f. sp. tritici reveals genes potentially involved in fungal differentiation.

The rust fungus Puccinia graminis f. sp. tritici is an obligately biotrophic pathogen on wheat plants and thus difficult to investigate. Hence, little is known about this fungus at the molecular level. We constructed a differential suppression subtractive hybridization cDNA-library from rust-infected vs. healthy wheat plants. The majority of expressed sequence tags (ESTs) showed similarities to fungal sequences. Semiquantitative RT-PCR using mRNA from rust-infected leaves, and from axenically grown, differentiating and nondifferentiating young rust colonies as well as sporulating and nonsporulating mature mycelia revealed rather diverse expression patterns for different ESTs, shedding new light on their potential involvement in differentiation and host-pathogen interaction.

Basidiomycota↗

PubMed2006

A functional variant in the CARD4 gene and risk of premature coronary heart disease.

Infection and innate immunity have been suggested as playing an important role in the pathogenesis of atherosclerosis. The recently discovered pattern-recognition receptor (PRR) proteins initiate signalling after host-pathogen interactions and several PRRs, especially the Toll-like receptor 4 (TLR4), have been shown to be involved in the development and progression of atherosclerosis. A new addition to the PRRs is CARD4, a gene that encodes the protein nucleotide-binding oligomerization domain 1 (NOD1) and that seems to be associated with barrier function in chronic inflammatory disorders. Recently, a functional variant in the CARD4 gene, the insertion-deletion polymorphism ND(1)+32656, has been associated with inflammatory barrier diseases (inflammatory bowel diseases and asthma). We analysed the frequencies of this known functional mutation in the CARD4 gene and of the two adjacent variants, rs2075822 and rs2907748, in a German sample of 1440 unrelated early onset coronary heart disease (CHD) patients and healthy controls. Genotype and haplotype data showed no evidence for a significant association of these CARD4 variants with CHD. Our results suggest that the analysed CARD4 mutations do not play a major role in the aetiology of CHD.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Common and contrasting themes of plant and animal diseases.

Recent studies in bacterial pathogenesis reveal common and contrasting mechanisms of pathogen virulence and host resistance in plant and animal diseases. This review presents recent developments in the study of plant and animal pathogenesis, with respect to bacterial colonization and the delivery of effector proteins to the host. Furthermore, host defense responses in both plants and animals are discussed in relation to mechanisms of pathogen recognition and defense signaling. Future studies will greatly add to our understanding of the molecular events defining host-pathogen interactions.

Amino Acid Sequence↗

PubMed2005

The genome of the kinetoplastid parasite, Leishmania major.

Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.

Animals↗

PubMed2006

Polymorphic secreted kinases are key virulence factors in toxoplasmosis.

The majority of known Toxoplasma gondii isolates from Europe and North America belong to three clonal lines that differ dramatically in their virulence, depending on the host. To identify the responsible genes, we mapped virulence in F(1) progeny derived from crosses between type II and type III strains, which we introduced into mice. Five virulence (VIR) loci were thus identified, and for two of these, genetic complementation showed that a predicted protein kinase (ROP18 and ROP16, respectively) is the key molecule. Both are hypervariable rhoptry proteins that are secreted into the host cell upon invasion. These results suggest that secreted kinases unique to the Apicomplexa are crucial in the host-pathogen interaction.

Alleles↗

PubMed2004

The domains of apoptosis: a genomics perspective.

Apoptosis plays important roles in many facets of normal physiology in animal species, including programmed cell death associated with fetal development or metamorphosis, tissue homeostasis, immune cell education, and some aspects of aging. Defects in the regulation of apoptosis contribute to multiple diseases associated with either inappropriate cell loss or pathological cell accumulation. Host-pathogen interactions have additionally provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses. To a large extent, the apoptosis machinery can be viewed as a network, with different nodes connected by physical interactions of evolutionarily conserved domains. These domains can serve as signatures for identification of proteins involved in the network. In particular, the caspase recruitment domains (CARDs); death effector domains (DEDs); death domains (DDs); BIR (baculovirus IAP repeat) domains of inhibitor of apoptosis proteins (IAPs); Bcl-2 family proteins; caspase protease domains; and endonuclease-associated CIDE (cell death-inducing DFF45-like effector) domains are found in common in proteins involved in apoptosis. In the genomes of mammals, genes encoding proteins that carry one or more of these signature domains are often present in multiple copies, making up diverse gene families that permit tissue-specific and highly regulated control of cell life and death decisions through combinations of stimulus-specific gene expression and complex protein interaction networks. In this Review, we organize the repertoire of apoptosis proteins of humans into domain families, drawing comparisons with homologs in other vertebrate and invertebrate animal species, and discuss some of the functional implications of these findings.

Animals↗

PubMed2006

Novel quantitative biosystem for modeling physiological fluid shear stress on cells.

The response of microbes to changes in the mechanical force of fluid shear has important implications for pathogens, which experience wide fluctuations in fluid shear in vivo during infection. However, the majority of studies have not cultured microbes under physiological fluid shear conditions within a range commonly encountered by microbes during host-pathogen interactions. Here we describe a convenient batch culture biosystem in which (i) the levels of fluid shear force can be varied within physiologically relevant ranges and quantified via mathematical models and (ii) large numbers of cells can be planktonically grown and harvested to examine the effect of fluid shear levels on microbial genomic and phenotypic responses. A quantitative model based on numerical simulations and in situ imaging analysis was developed to calculate the fluid shear imparted by spherical beads of different sizes on bacterial cell cultures grown in a rotating wall vessel (RWV) bioreactor. To demonstrate the application of this model, we subjected cultures of the bacterial pathogen Salmonella enterica serovar Typhimurium to three physiologically-relevant fluid shear ranges during growth in the RVW and demonstrated a progressive relationship between the applied fluid shear and the bacterial genetic and phenotypic responses. By applying this model to different cell types, including other bacterial pathogens, entire classes of genes and proteins involved in cellular interactions may be discovered that have not previously been identified during growth under conventional culture conditions, leading to new targets for vaccine and therapeutic development.

Bacterial Proteins↗

PubMed1998

Closely related plasmid replicons coexisting in the phytopathogen pseudomonas syringae show a mosaic organization of the replication region and altered incompatibility behavior

Many Pseudomonas syringae strains contain native plasmids that are important for host-pathogen interactions, and most of them contain several coexisting plasmids (pPT23A-like plasmids) that cross-hybridize to replication sequences from pPT23A, which also carries a gene cluster coding for the phytotoxin coronatine in P. syringae pv. tomato PT23. In this study, three functional pPT23A-like replicons were cloned from P. syringae pv. glycinea race 6, suggesting that the compatibility of highly related replicons is a common feature of P. syringae strains. Hybridization experiments using three separate incompatibility determinants previously identified from pPT23A and the rulAB (UV radiation tolerance) genes showed that the organization of the replication region among pPT23A-like plasmids from several P. syringae pathovars is poorly conserved. The putative repA gene from four pPT23A-like replicons from P. syringae pv. glycinea race 6 was amplified by using specific primers. The restriction profiles of the resulting PCR products for the race 6 plasmids were more similar to each other than they were to that of pPT23A. These data, together with the existence of other cross-hybridizing DNA regions around the replicon among the race 6 pPT23A-like plasmids, suggest that some of these plasmids may have originated from duplication events. Our results also imply that modifications of the repA sequences and the poor conservation of putative maintenance determinants contribute to the suppression of incompatibility among members of the pPT23A-like family, thus enhancing the genomic plasticity of P. syringae.

Journal Article↗

PubMed2001

Stress and stress-induced neuroendocrine changes increase the susceptibility of juvenile oysters (Crassostrea gigas) to Vibrio splendidus.

Oysters are permanently exposed to various microbes, and their defense system is continuously solicited to prevent accumulation of invading and pathogenic organisms. Therefore, impairment of the animal's defense system usually results in mass mortalities in cultured oyster stocks or increased bacterial loads in food products intended for human consumption. In the present study, experiments were conducted to examine the effects of stress on the juvenile oyster's resistance to the oyster pathogen Vibrio splendidus. Oysters (Crassostrea gigas) were challenged with a low dose of a pathogenic V. splendidus strain and subjected to a mechanical stress 3 days later. Both mortality and V. splendidus loads increased in stressed oysters, whereas they remained low in unstressed animals. Injection of noradrenaline or adrenocorticotropic hormone, two key components of the oyster neuroendocrine stress response system, also caused higher mortality and increased accumulation of V. splendidus in challenged oysters. These results suggest that the physiological changes imposed by stress, or stress hormones, influenced host-pathogen interactions in oysters and increased juvenile C. gigas vulnerability to Vibrio splendidus.

Adrenocorticotropic Hormone↗

PubMed2004

The P450 monooxygenase BcABA1 is essential for abscisic acid biosynthesis in Botrytis cinerea.

The phytopathogenic ascomycete Botrytis cinerea is known to produce abscisic acid (ABA), which is thought to be involved in host-pathogen interaction. Biochemical analyses had previously shown that, in contrast to higher plants, the fungal ABA biosynthesis probably does not proceed via carotenoids but involves direct cyclization of farnesyl diphosphate and subsequent oxidation steps. We present here evidence that this "direct" pathway is indeed the only one used by an ABA-overproducing strain of B. cinerea. Targeted inactivation of the gene bccpr1 encoding a cytochrome P450 oxidoreductase reduced the ABA production significantly, proving the involvement of P450 monooxygenases in the pathway. Expression analysis of 28 different putative P450 monooxygenase genes revealed two that were induced under ABA biosynthesis conditions. Targeted inactivation showed that one of these, bcaba1, is essential for ABA biosynthesis: DeltaBcaba1 mutants contained no residual ABA. Thus, bcaba1 represents the first identified fungal ABA biosynthetic gene.

Abscisic Acid↗

PubMed2005

Phylogenetic characterization of virulence and resistance phenotypes of Pseudomonas syringae.

Individual strains of the plant pathogenic bacterium Pseudomonas syringae vary in their ability to produce toxins, nucleate ice, and resist antimicrobial compounds. These phenotypes enhance virulence, but it is not clear whether they play a dominant role in specific pathogen-host interactions. To investigate the evolution of these virulence-associated phenotypes, we used functional assays to survey for the distribution of these phenotypes among a collection of 95 P. syringae strains. All of these strains were phylogenetically characterized via multilocus sequence typing (MLST). We surveyed for the production of coronatine, phaseolotoxin, syringomycin, and tabtoxin; for resistance to ampicillin, chloramphenicol, rifampin, streptomycin, tetracycline, kanamycin, and copper; and for the ability to nucleate ice at high temperatures via the ice-nucleating protein INA. We found that fewer than 50% of the strains produced toxins and significantly fewer strains than expected produced multiple toxins, leading to the speculation that there is a cost associated with the production of multiple toxins. None of these toxins was associated with host of isolation, and their distribution, relative to core genome phylogeny, indicated extensive horizontal genetic exchange. Most strains were resistant to ampicillin and copper and had the ability to nucleate ice, and yet very few strains were resistant to the other antibiotics. The distribution of the rare resistance phenotypes was also inconsistent with the clonal history of the species and did not associate with host of isolation. The present study provides a robust phylogenetic foundation for the study of these important virulence-associated phenotypes in P. syringae host colonization and pathogenesis.

Adaptation, Physiological↗