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Results for “host:pathogen interactions”

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At least 217 records · Page 12Linked to original sources

PubMed2026

Modeling reptile virus infection in vitro using Python regius airway organoids.

Zoonoses pose substantial global health risks, highlighting the need to better understand animal-to-human transmission. Reptiles are increasingly recognized as hosts of diverse pathogens, including numerous viruses, yet the diversity and prevalence of reptile pathogens, as well as their potential risk to humans, remain poorly understood. Here, we establish and characterize airway organoids derived from Python regius, providing an in vitro model to study reptile airway infection. Through de novo assembly of a Python regius reference genome, we characterize airway organoids at single-cell resolution, which suggests the presence of diverse cell populations including ionocytes, ciliated, secretory, goblet, endocrine, tuft, and basal cells. The organoids support productive infection with Ball Python Nidovirus (BPNV) and mount a robust epithelial antiviral response through the induction of interferon-stimulated genes, cytokines, and genes involved in chemical defense. As a proof-of-concept, treating organoids with antiviral drugs during infection reduces BPNV levels, highlighting the model's utility for drug testing. By providing a reductionist system of the serpentes airway, these organoids constitute a physiologically relevant in vitro model to study reptile viruses and host-pathogen interactions in their native host.

Animals↗

PubMed2004

The role of plant cell wall polysaccharide composition in disease resistance.

The high degree of structural complexity of plant cell wall polysaccharides has led to suggestions that some components might function as latent signal molecules that are released during pathogen infections and elicit defensive responses by the plant. However, there has been a paucity of genetic evidence supporting the idea that variation in cell wall composition plays a role in the outcome of host-pathogen interactions. Recently, several genetic studies have provided new lines of evidence implicating cell wall polysaccharides as factors in host-pathogen interactions.

Cell Wall↗

PubMed2026

Human genetic variation associates with infection by derived Ugandan M. tuberculosis lineage.

BACKGROUND: Several studies have examined host and pathogen genetic influences on tuberculosis (TB) susceptibility separately, but relatively few studied their combined effects. However, host-pathogen interactions or co-evolution may explain the inability to replicate many reported human genetic effects across global populations and provide additional insight into TB risk. In this study, we address such possible interactions by focusing on the outcome of infection with the L4-Uganda M. tuberculosis sub-lineage and human genetic variants as independent variables. This is possible because the L4-Uganda sub-lineage is both restricted to Uganda and nearby locations and is recent there, compared to other more ancestral L4 lineages. METHODS: Our study consisted of 276 culture-confirmed adult TB cases from a long-standing household contact study. We conducted a genome-wide association study, with infection with L4-Uganda versus L4-NonUganda as the outcome. RESULTS: Multiple loci with results suggestive of association (p<10-5) also demonstrated convergent relevant evidence for strain specific infection via: evidence of gene expression in relevant cells and lung tissue, signatures of natural selection, eQTL expression, and CRISPR screens for immunity-related genes. We also replicated previously published host-pathogen interaction effects, demonstrating that effects seen for other sub-lineages were also present for L4-Uganda. CONCLUSIONS: These results provide evidence for host-pathogen co-evolution in TB, consistent with our previous work, and indicate these interactions involve genes highly relevant to the host immune response to Mycobacterium infection.

GWAS↗

PubMed2005

SuperSAGE.

The application of transcriptomics to study host-pathogen interactions has already brought important insights into the mechanisms of pathogenesis, and is expanding further keeping pace with the accumulation of genomic sequences of host organisms (human and economically important organisms such as food crops) and their pathogens (viruses, bacteria, fungi and protozoa). In this review, we introduce SuperSAGE, a substantially improved variant of serial analysis of gene expression (SAGE), as a potent tool for the transcriptomics of host-pathogen interactions. Notably, the generation of 26 bp tags in the SuperSAGE procedure allows to decipher the 'interaction transcriptome', i.e. the simultaneous monitoring of quantitative gene expression, of both a host and one of its eukaryotic pathogens. The potential of SuperSAGE tags for a rapid functional analysis of target genes is also discussed.

Animals↗

PubMed1998

Flow cytometry and bacterial pathogenesis.

Our understanding of microbial adaptations to diverse and threatening environments is limited by the assumption that the behavior of individual bacteria can be accurately determined by measuring the behavior of populations. Recent advances in gene expression reporter systems, fluorescence microscopy and flow cytometry allow microbiologists to explore the complex interactions between bacteria and their environment with single cell resolution. The application of these technologies has been particularly useful in systems, such as host-pathogen interactions, where genetic analysis is often cumbersome. Recently, flow cytometry is increasingly being applied to study host-pathogen interactions.

Bacterial Infections↗

PubMed1999

Pathogen-tick-host interactions: Borrelia burgdorferi and TBE virus.

Both tick-borne encephalitis (TBE) virus and Borrelia burgdorferi depend for their survival on a tick-borne transmission cycle involving diverse vertebrate hosts and ixodid (primarily Ixodes) tick species. Increasing evidence strongly suggests that a key factor in successful transmission is the ability of these pathogens to exploit the pharmacological properties of their vector tick's saliva. Proteins and other chemicals, secreted in tick saliva, control the vertebrate hosts' haemostatic, inflammatory and immune responses in order to facilitate blood-feeding. Such bioactive saliva molecules include immunoglobulin-binding proteins, histamine-binding proteins, natural killer cell and interferon regulators, and complement inhibitors. By unravelling the contents of tick saliva and understanding their interactions with host and pathogen, we may identify new strategies for disease control.

Animals↗

PubMed2004

Pharmacogenomic strategies against resistance development in microbial infections.

There are several promising new strategies against resistance development in microbial infections. This paper discusses typical experimental and bioinformatical strategies to study the impact of infectious challenges on host-pathogen interaction, followed by several novel approaches and sources for new pharmaceutical strategies against resistance development. Genomics reveals promising new targets by providing a better understanding of cellular pathways, through the identification of new pathways, and by identifying new intervention areas, such as phospholipids, glycolipids, innate immunity, and antibiotic peptides. Additional antibiotic resources come from new genomes, including marine organisms, lytic phages and probiotic strategies. A system perspective regards all interactions between the host, pathogen and environment to develop new pharmacogenomic strategies against resistance development.

Animals↗

PubMed2025

Genome-to-genome analysis reveals associations between human and mycobacterial genetic variation in tuberculosis patients from Tanzania.

The risk and prognosis of tuberculosis (TB) are influenced by a complex interplay between human and bacterial genetic factors. While previous genomic studies have largely examined human and bacterial genomes separately, we adopted an integrated approach to uncover host-pathogen interactions. We leveraged paired human and Mycobacterium tuberculosis (M.tb) genomic data from 1000 adult TB patients from Tanzania and used a "genome-to-genome" approach to search for associations between human and M.tb genetic variants and to identify interacting genetic loci. Our analyses revealed two significant host-pathogen genetic associations. The first significant association (p = 4.7e-11) links a human intronic variant in PRDM15 (rs12151990), a gene involved in apoptosis regulation, with an M.tb variant in Rv2348c (I101M), which encodes a T cell-stimulating antigen. The second significant association (p = 6.3e-11) connects a human intergenic variant near TIMM21 and FBXO15 (rs75769176) - also associated with TB severity (p = 0.04) - with an M.tb variant in FixA (T67M). While FBXO15 is involved in the regulation of antigen processing and TIMM21 affects mitochondrial function, FixA's role remains undefined due to limited functional characterization. Additionally, we observed that a group of M.tb T cell epitope variants were significantly associated with HLA-DRB1 variation, suggesting that, despite their rarity, certain epitopes may still be subjected to immune selective pressure. Together, these findings identify previously unknown sites of genomic conflicts between humans and M.tb, advancing our understanding of how this pathogen evades selection pressure and persist in human populations.

Humans↗

PubMed1989

The potential role of pathogens in biological control.

It is now well established that pathogens such as viruses, fungi bacteria and protozoans can have profound effects on the dynamics of their invertebrate host populations. Theoretical models of invertebrate host-pathogen interactions which assume uniform structure of the pathogen population may reasonably explain the oscillatory behaviour observed in some systems, but do not adequately describe the existence of more constant populations found in other host-pathogen interactions. An examination of the literature relating to these relatively stable systems suggests that the common thread is the eventual transmission of some of the more protected, longer-lived stages of the pathogen occurring in reservoirs, such as the soil, host cadavers on trees, or the live host itself. In this letter, I propose a new theoretical model which incorporates this population structure and accounts for the range of dynamics observed in natural systems. In particular, I show that host populations may be regulated to low and relatively constant densities if sufficient numbers of pathogens are trans-located from pathogen reservoirs to habitats where transmission can occur. An understanding of pathogen reservoirs may be of value in the design of biological control programmes and may greatly increase the effectiveness of pathogens as biological control agents.

Animals↗

PubMed2006

Anaplasmosis: focusing on host-vector-pathogen interactions for vaccine development.

Anaplasma marginale and A. phagocytophylum are intracellular rickettsiae that cause bovine anaplasmosis and human granulocytic anaplasmosis, respectively. The ultimate vaccine for the control of anaplasmosis would be one that reduces infection and transmission of the pathogen by ticks. Effective vaccines for control of anaplasmosis are not available despite attempts using different approaches, such as attenuated strains, infected erythrocyte and tick cell-derived purified antigens, and recombinant pathogen and tick-derived proteins. Three lines of functional analyses were conducted by our laboratory to characterize host-tick-Anaplasma interactions to discover potential vaccine candidate antigens to control tick infestations and the infection and transmission of Anaplasma spp.: (1) characterization of A. marginale adhesins involved in infection and transmission of the pathogen, (2) global expression analysis of genes differentially expressed in HL-60 human promyelocytic cells in response to infection with A. phagocytophilum, and (3) identification and characterization of tick-protective antigens by expression library immunization (ELI) and analysis of expressed sequence tags (EST) in a mouse model of tick infestations and by RNA interference in ticks. These experiments have resulted in the characterization of the A. marginale MSP1a as an adhesin for bovine erythrocytes and tick cells, providing support for its use as candidate vaccine antigen for the control of bovine . Microarray analysis of genes differentially expressed in human cells infected with A. phagocytophilum identified key molecules involved in pathogen infection and multiplication. The screening for tick-protective antigens resulted in vaccine candidates reducing tick infestation, molting, and oviposition and affecting Anaplasma infection levels in ticks.

Anaplasmosis↗

PubMed2001

Evolution of pathogen virulence: the role of variation in host phenotype.

Selection on pathogens tends to favour the evolution of growth and reproductive rates and a concomitant level of virulence (damage done to the host) that maximizes pathogen fitness. Yet, because hosts often pose varying selective environments to pathogens, one level of virulence may not be appropriate for all host types. Indeed, if a level of virulence confers high fitness to the pathogen in one host phenotype but low fitness in another host phenotype, alternative virulence strategies may be maintained in the pathogen population. Such strategies can occur either as polymorphism, where different strains of pathogen evolve specialized virulence strategies in different host phenotypes or as polyphenism, where pathogens facultatively express alternative virulence strategies depending on host phenotype. Polymorphism potentially leads to specialist pathogens capable of infecting a limited range of host phenotypes, whereas polyphenism potentially leads to generalist pathogens capable of infecting a wider range of hosts. Evaluating how variation among hosts affects virulence evolution can provide insight into pathogen diversity and is critical in determining how host pathogen interactions affect the phenotypic evolution of both hosts and pathogens.

Biological Evolution↗

PubMed2001

Host and pathogen interaction during vaginal infection by Trichomonas vaginalis and Mycoplasma hominis or Ureaplasma urealyticum.

Vaginal infections by Trichomonas vaginalis and Mycoplasma hominis have been shown to be associated. Since M. hominis and Ureaplasma urealyticum are similar pathogens, both belonging to the class of the mycoplasmata, we describe here a molecular study into the interdependence of U. urealyticum and T. vaginalis during infection. Susceptibility towards infection by U. urealyticum depends on genetic polymorphism in the interleukin-1 receptor antagonist (IL-1RA) gene. Now, we defined the relation between IL-1RA genotypes and infection by M. hominis and T. vaginalis. Finally, we also developed a restriction fragment length polymorphism (RFLP) tool for mapping variation in the T. vaginalis AP33 adhesin in order to define putative associations between parasite subtype and mycoplasmata or host. Studies using crudepellets from T. vaginalis culture broth clearly confirm the association between T. vaginalis and M. hominis infection. The association between IL-1RA genotype 2,2 and lack of U. urealyticum infection is corroborated as well. U. urealyticum infection and infection by T. vaginalis are independent. Furthermore, T. vaginalis and M. hominis infection are not depending on IL-1RA genotypes. Interestingly, one of the three AP33 RFLP types identified appeared to be associated with the absence of U. urealyticum infection. In conclusion, the complex interaction between bacterial and parasitic pathogens and the infected host is determined by genetic characteristics of host and microorganisms involved.

Adult↗

PubMed2001

The basic depression ratio of the host: the evolution of host resistance to microparasites.

The basic reproduction ratio R0 occupies a central position in the theory of host pathogen interactions. However, this quantity stresses the role of the pathogen. This paper proposes an additional, more host-centred char acterization using the basic depression ratio D0. This quantity is the number of host individuals per infected by which the infected host population is depressed below its uninfected level. This paper shows that a baseline criterion for the evolution of host resistance to microparasites is that resistance evolves to minimize D0. This parallels the result for pathogen virulence where R0 is maximized. The tension between these two criteria is noted. The framework established allows a discussion of trade-offs between aspects of the pathogen-free host biology and the host pathogen interaction. For certain linear and convex trade-offs it is shown that the strain with the lowest transmission parameter beta wins (despite the fact that it has the lowest intrinsic birth rate a). For corresponding concave trade-offs, either the strain with minimum beta and a or the strain with maximum beta and a wins. Finally the connection with the techniques of adaptive dynamics is made. Evolutionary singular points are shown to occur at extrema of D0. The evolutionary attainment of the results is discussed.

Adaptation, Physiological↗

PubMed2006

Host-virus interaction: a new role for microRNAs.

MicroRNAs (miRNAs) are a new class of 18-23 nucleotide long non-coding RNAs that play critical roles in a wide spectrum of biological processes. Recent reports also throw light into the role of microRNAs as critical effectors in the intricate host-pathogen interaction networks. Evidence suggests that both virus and hosts encode microRNAs. The exclusive dependence of viruses on the host cellular machinery for their propagation and survival also make them highly susceptible to the vagaries of the cellular environment like small RNA mediated interference. It also gives the virus an opportunity to fight and/or modulate the host to suite its needs. Thus the range of interactions possible through miRNA-mRNA cross-talk at the host-pathogen interface is large. These interactions can be further fine-tuned in the host by changes in gene expression, mutations and polymorphisms. In the pathogen, the high rate of mutations adds to the complexity of the interaction network. Though evidence regarding microRNA mediated cross-talk in viral infections is just emerging, it offers an immense opportunity not only to understand the intricacies of host-pathogen interactions, and possible explanations to viral tropism, latency and oncogenesis, but also to develop novel biomarkers and therapeutics.

Eukaryotic Cells↗

PubMed2003

Rapid induction of a protein disulfide isomerase and defense-related genes in wheat in response to the hemibiotrophic fungal pathogen Mycosphaerella graminicola.

Mycosphaerella graminicola, incitant of septoria tritici blotch, is a widespread and significant pathogen of wheat that is not closely related to other fungi being developed as genetic models for host-pathogen interactions. Several resistance genes in wheat have been identified, yet the molecular mechanisms of resistance are unknown. To identify host genes involved in the resistance response, expression profiles of the wheat line Tadinia (containing the Stb4 gene for resistance) and the susceptible line Yecora Rojo, non-inoculated or inoculated with M. graminicola, were compared by differential-display polymerase chain reaction (DD-PCR). Among the differentially expressed genes was a protein disulfide isomerase (PDI), which is well known as a molecular chaperone and component of signal-transduction pathways in animal systems but had not been implicated previously in plant defense response. Real-time quantitative reverse-transcription PCR and northern analysis revealed that PDI was induced within 3 h of inoculation with highest induction in the pathogen-treated resistant lines. These responses of PDI were similar to the early and strong resistance-related responses displayed by the pathogenesis-related (PR) proteins, PR-1, PR-2 and PR-5. In contrast, a wheat lipoxygenase was down-regulated in the resistant lines at time points corresponding with peak induction of the PR genes. Thus, part of the resistance mechanism may involve repression of a gene that could otherwise aid fungal growth. Wheat responds much more rapidly than believed previously to signals produced by M.graminicola. These early responses begin prior to penetration of the host and appear to determine the outcome of the host-pathogen interaction.

Ascomycota↗

PubMed2002

Staphylococcus aureus aconitase inactivation unexpectedly inhibits post-exponential-phase growth and enhances stationary-phase survival.

Staphylococcus aureus preferentially catabolizes glucose, generating pyruvate, which is subsequently oxidized to acetate under aerobic growth conditions. Catabolite repression of the tricarboxylic acid (TCA) cycle results in the accumulation of acetate. TCA cycle derepression coincides with exit from the exponential growth phase, the onset of acetate catabolism, and the maximal expression of secreted virulence factors. These data suggest that carbon and energy for post-exponential-phase growth and virulence factor production are derived from the catabolism of acetate mediated by the TCA cycle. To test this hypothesis, the aconitase gene was genetically inactivated in a human isolate of S. aureus, and the effects on physiology, morphology, virulence factor production, virulence for mice, and stationary-phase survival were examined. TCA cycle inactivation prevented the post-exponential growth phase catabolism of acetate, resulting in premature entry into the stationary phase. This phenotype was accompanied by a significant reduction in the production of several virulence factors and alteration in host-pathogen interaction. Unexpectedly, aconitase inactivation enhanced stationary-phase survival relative to the wild-type strain. Aconitase is an iron-sulfur cluster-containing enzyme that is highly susceptible to oxidative inactivation. We speculate that reversible loss of the iron-sulfur cluster in wild-type organisms is a survival strategy used to circumvent oxidative stress induced during host-pathogen interactions. Taken together, these data demonstrate the importance of the TCA cycle in the life cycle of this medically important pathogen.

Acetates↗

PubMed2006

Imaging today's infectious animalcules.

The study of pathogens and their interactions with host cells has advanced hand-in-hand with developments in optical microscopy. Whereas microbiology benefits enormously from modern imaging technologies, for example, digital imaging and confocal microscopy, it also presents unique challenges. To overcome these, microbiologists are adept at customising imaging methods, and recently there have been studies using state-of-the-art quantitative imaging methods to probe host-pathogen interactions at the single-cell level. Of particular interest are the studies using combined light and electron microscopy methods, bi-arsenical tetra-cysteine tag labelling and automated image-acquisition and analysis for high-throughput/high-content experimentation. These applications demonstrate how imaging methodologies, adapted for microbiology, continue to open avenues for studies that previously have proven inaccessible.

Animals↗

PubMed2004

Two-dimensional reference map of Candida albicans hyphal forms.

We have set up an in vitro model of culture of Candida albicans fungal cells that mimics the physiological conditions found in human beings in order to carry out studies of host-pathogen interaction. Under these conditions, C. albicans undergoes dimorphic transition (yeast-hyphae); this morphological change has been proposed as a virulence factor for this fungus. C. albicans cytoplasmic extract from hyphae cells was analyzed by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and a reference map was obtained. Protein identification was carried out by peptide mass fingerprinting or sequence tagging using a matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) or a MALDI-TOF/TOF mass spectrometer. A total of 106 spots, excised from 2-D gels, were analyzed. This resulted in the identification of 43 proteins involved in metabolism, 13 involved in transcription, protein synthesis, and fate, 8 involved in cell rescue, virulence, and defense, and 2 proteins of unknown function. This reference map is an important tool for future studies of protein differential expression after host-pathogen interaction.

Candida albicans↗