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Results for “host:pathogen interactions”

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PubMed1980

Ultrastructural observations on cellular and subcellular aspects of experimental Mycoplasma pneumoniae disease.

The ultrastructural organization of Mycoplasma pneumoniae membranes and spatial relationships of this pathogen to epithelial cells in tracheal organ cultures were examined ultrastructurally by freeze-fracture techniques. Areas of morphologically distinct cell membrane variability characterized by membrane blebs and altered distributions of membrane associated particles were observed in replicas of M. pneumoniae cells. Inspection of the host tracheal epithelium demonstrated the alignment of M. pneumoniae to the epithelium with an accompanying deterioration in the integrity of the lumenal surface membranes and subsequent loss of the epithelial cell cytosol. Ciliary dysfunction was suggested by the observation of ciliary lesions and of disorganized epithelial cell cilia. The methodology used in these studies has permitted a new perspective of host-pathogen interactions at both the cellular and subcellular levels in tracheal organ cultures. These studies may also illustrate ultrastructural correlates of the alteration of host macromolecular synthesis in experimental M. pneumoniae infection.

Animals↗

PubMed2006

Directed delivery of heat-labile enterotoxin by enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC), leading causes of diarrhoeal morbidity and mortality in developing countries, are heterogenous pathogens that elaborate heat-labile (LT) and/or heat-stable (ST) enterotoxins which elicit watery, cholera-like diarrhoea. The molecular events permitting efficient delivery of LT remain undefined. Here, we characterize the role of host-pathogen interaction as it relates to the delivery of LT by ETEC. Separation of bacteria from target intestinal epithelial monolayers by semipermeable filters prevented activation of adenylate cyclase suggesting that pathogen-host cell contact is required for efficient toxin delivery. Likewise, a non-motile strain bearing a mutation in the flagellar fliD gene was deficient in delivery of LT relative to the ETEC (H10407) prototype. Although LT secretion via the type II secretion system (T2SS) was responsive to a variety of environmental factors, neither toxin release nor delivery depended on transcriptional activation of genes encoding LT or the T2SS. Fusions of green fluorescent protein to GspM (a component of the T2SS system for LT) and to LT demonstrated that both T2SS and toxin are distributed at one pole of the ETEC bacterium. Optimal LT delivery may occur in a polarized fashion with transfer of preformed toxin upon close interaction with host cells, preventing neutralization of LT.

Caco-2 Cells↗

PubMed2001

A role for salicylic acid and NPR1 in regulating cell growth in Arabidopsis.

Salicylic acid (SA) plays a key role in activating defenses and cell death during plant-pathogen interactions. In response to some pathogens, SA also limits the extent of cell death, indicating that it acts positively or negatively depending on the host-pathogen interaction. In addition, we previously showed that SA affects cell growth in the Arabidopsis defense-related mutants accelerated cell death 6-1 (acd6-1) and aberrant growth and death 2 (agd2). Using acd6-1, agd2 and two other defense-related mutants, lesion simulating disease 6 (lsd6), suppressor of SA-insensitivity (ssi1), we show here in detail that SA regulates cell growth by specifically affecting cell enlargement, endoreduplication and/or cell division. We find that SA can act either positively or negatively to regulate cell growth depending on the context in which signaling occurs. Additionally, Nonexpressor of PR 1 (NPR1), a key SA signaling protein important for regulating defenses and cell death, also acts to promote cell division and/or suppress endoreduplication during leaf development. We propose that SA interacts with multiple receptors or signaling pathways to control cellular alterations during normal development, pathogen attack and/or stress situations. We suggest that SA and NPR1 play broader roles in cell fate control than has previously been understood.

Arabidopsis↗

PubMed2004

Differential gene expression in mononuclear phagocytes infected with pathogenic and non-pathogenic mycobacteria.

The pathogenic mycobacteria are an insidious group of bacterial pathogens that cause the deaths of millions of people every year. One of the reasons these pathogens are so successful is that they are able to invade and replicate within host macrophages, one of the first lines of defence against intruding pathogens. In contrast, non-pathogenic mycobacteria, such as Mycobacterium smegmatis are killed rapidly by macrophages. In order to understand better the series of events that allow pathogenic mycobacteria to survive and replicate within macrophages, while the non-pathogenic mycobacteria are killed rapidly, we inoculated the human monocytic cell line U937 with pathogenic (M. tuberculosis and M. avium) and non-pathogenic (M. smegmatis) mycobacteria and monitored the expression of over 3500 genes at 4, 12 and 24 h post-inoculation using a commercially available gene array system. We observed multiple differences in the gene expression patterns of monocytes infected with pathogenic and non-pathogenic mycobacteria including genes involved in cytokine, lymphokine and chemokine production, adhesion, apoptosis, signal transduction, transcription, protein cleavage, actin polymerization and growth. We also observed differences in gene expression profiles in monocytes infected with M. tuberculosis or M. avium, indicating that there are differences in the host pathogen interactions of mononuclear phagocytes infected with different pathogenic mycobacterial species. These results increase the understanding of the mechanisms used by pathogenic mycobacteria to cause disease, the host response to these organisms, and provide new insights for antimycobacterial intervention strategies.

Gene Expression Regulation↗

PubMed2004

Mast cells at the host-pathogen interface: host-protection versus immune evasion in leishmaniasis.

Infection of a susceptible host with Leishmania, a protozoan parasite, causes the disease leishmaniasis, which is characterized by neutrophil, eosinophil, macrophage, lymphocyte and mast cell infiltration into the infected tissue followed by parasite growth. Although the roles played by other cells in leishmaniasis are known, the role of mast cells remains to be ascertained. Here, we demonstrate that Leishmania regulates mast cell infiltration to the site of infection, mast cell production and mast cell function resulting in differential growth of the parasite in resistant (C57BL/6 or CBA/T6T6) and susceptible (BALB/c) macrophages. An interleukin-3-dependent augmentation in mast cell committed progenitors is observed in BALB/c but not in C57BL/6 mice during Leishmania infection. The mast cell supernatants inhibit IFN-gamma-dependent restriction of Leishmania growth in macrophages in BALB/c mice whereas the reverse phenomenon occurs in C57BL/6 mice. Our data reveals a different facet of host-pathogen interaction.

Animals↗

PubMed1984

Differential induction of chalcone synthase mRNA activity at the onset of phytoalexin accumulation in compatible and incompatible plant-pathogen interactions.

Changes in the mRNA activity of chalcone synthase, the first enzyme of phenylpropanoid metabolism specific to flavonoid/isoflavonoid biosynthesis, have been investigated in relation to expression of the phytoalexin defense response in race-cultivar specific interactions between hypocotyls of Phaseolus vulgaris and the partially biotrophic fungus Colletotrichum lindemuthianum, causal agent of anthracnose. In an incompatible interaction (host resistant) there is an early but localized increase in chalcone synthase mRNA activity prior to the onset of accumulation of the phenylpropanoid-derived phytoalexin phaseoflin and expression of hypersensitive resistance. In contrast, in a compatible interaction (host susceptible) there is no induction of mRNA activity in the early stages of infection but rather a delayed, widespread increase during attempted lesion limitation at the onset of symptom development. The data indicate that control of phytoalexin gene expression is a key early component in the defense responses of biologically stressed cells during a race-cultivar specific host-pathogen interaction.

Journal Article↗

PubMed1998

Internalization and cytotoxicity are important virulence mechanisms in Vibrio-fish epithelial cell interactions.

Vibrio anguillarum and Vibrio damselae are Gram-negative bacteria that cause systemic infections called vibriosis in fish. They can enter fish cells and survive as intracellular parasites. The host-pathogen interactions between these Vibrio species and the fish epithelial cell lines epithelioma papillosum of carp (EPC) and grunt-fin tissue (GF) cells, were examined using phase-contrast, scanning electron and confocal microscopy. In addition, potential signal transduction pathways that precede bacterial internalization were studied by using signal transduction inhibitors. Some Vibrio species induced morphological changes in fish cells and this allowed classification into a cytopathic group and a noncytopathic group. The cytopathic group could be subdivided into two invasive groups (I and II) and a cytotoxic group. Of the invasive strains V. anguillarum 811218-5W (group I) and G/Virus/5(3) (group II), genistein, a tyrosine kinase inhibitor, only inhibited internalization of V. anguillarum G/Virus/5(3) into EPC cells, whereas staurosporine, a protein kinase C inhibitor, accelerated internalization of both strains. Cytochalasin D, an inhibitor of microfilament polymerization, prevented internalization of both strains, whilst vincristin, a microtubule inhibitor, only inhibited internalization of V. anguillarum G/Virus/5(3). For the cytotoxic strain V. damselae ATCC 33539, extracellular products (ECP) alone caused morphological changes in EPC and GF. Bacterial internalization may not be important in the pathogenesis of this group. The non-cytopathic strain V. anguillarum S2/5/93(2) did not enter cells or induce any changes in EPC and GF monolayers. This study has identified some major differences between Vibrio species in their interactions with fish cells in vitro and will thus facilitate future studies of the molecular basis of pathogenesis of vibriosis.

Animals↗

PubMed2006

Nucleotide-binding oligomerization domain-1 and epidermal growth factor receptor: critical regulators of beta-defensins during Helicobacter pylori infection.

Host-pathogen interactions that allow Helicobacter pylori to survive and persist in the stomach of susceptible individuals remain unclear. Human beta-defensins (hBDs), epithelial-derived antimicrobial peptides are critical components of host-defense at mucosal surfaces. The role of H. pylori-mediated NF-kappaB and epidermal growth factor receptor (EGFR) activation on beta-defensin expression was investigated. Transient transfection studies utilizing beta-defensin promoter constructs were conducted in gastric cells with contribution of individual signaling events evaluated by the addition of specific inhibitors, small interference nucleotide-binding oligomerization domain 1 (NOD1) RNA or plasmids encoding Vaccinia virus proteins that interrupt interleukin-1 and Toll-like receptor signaling. The role of individual MAPK pathways was further delineated in HEK-293 cells expressing conditional MAPK mutants. We found hBD2 expression exclusively dependent on the presence of the bacterial cag pathogenicity island, with NOD1 a critical host sensor. Impairment of murinebeta-defensin 4 (an orthologue of hBD2) expression in NOD1-deficient mice 7-days post-infection further confirmed the role of this cytoplasmic pattern-recognition receptor in eliciting host innate immunity. In contrast to hBD2, hBD3 expression was NOD1-independent but EGFR and ERK pathway-dependent. Importantly, Toll-like receptor signaling was not implicated in H. pylori-mediated hBD2 and hBD3 gene expression. The divergent signaling events governing hBD2 and hBD3 expression suggest temporal functional variation, such that hBD2 may contribute to antimicrobial barrier function during the inflammatory phase with hBD3 playing a greater role during the repair, wound healing phase of infection.

Animals↗

PubMed2007

Seasonality of infectious diseases.

Seasonality, a periodic surge in disease incidence corresponding to seasons or other calendar periods, characterizes many infectious diseases of public health importance. The recognition of seasonal patterns in infectious disease occurrence dates back at least as far as the Hippocratic era, but mechanisms underlying seasonality of person-to-person transmitted diseases are not well understood. Improved understanding will enhance understanding of host-pathogen interactions and will improve the accuracy of public health surveillance and forecasting systems. Insight into seasonal disease patterns may be gained through the use of autocorrelation methods or construction of periodograms, while seasonal oscillation of infectious diseases can be easily simulated using simple transmission models. Models demonstrate that small seasonal changes in host or pathogen factors may be sufficient to create large seasonal surges in disease incidence, which may be important particularly in the context of global climate change. Seasonality represents a rich area for future research.

Communicable Diseases↗

PubMed2000

Tropical environments, human activities, and the transmission of infectious diseases.

Throughout recent history, the tropical regions of the world have been affected more severely by infectious diseases than the temperate world. Much of the success of infectious diseases in that region is due to both biological and environmental factors that encourage high levels of biodiversity in hosts, vectors, and pathogens, and social factors that compromise efforts to control diseases. Several of these factors are described. Discussion then shifts to specific types of host-pathogen relationships. The most important of these in the tropics is the relationship between humans, a pathogen, and a vector that carries the pathogen from one human to another. Mosquitoes are the vector responsible for the transmission of many vector-borne human diseases. Characteristics of mosquito-human interactions are described, including cultural behaviors humans have developed that both increase the chances of transmission and help to limit that transmission. The transmission of water-borne diseases, fecal-oral transmission, zoonotic diseases, respiratory illnesses, and sexually transmitted diseases are also discussed. Attention is paid to how diseases with these modes of transmission differ in characteristics and importance in tropical human populations compared to those in temperate regions. Following this general discussion, three case studies are presented in some detail. The diseases chosen for the case studies include cholera, lymphatic filariasis, and dracunculiasis (guinea worm). These three case studies taken together provide examples of the diversity of human host-pathogen interactions as well as ways that human activities have both promoted their spread and helped to control them. The transmission of all three diseases is related to the nature and quality of water sources. The transmission of cholera, a water-borne disease, is related to sanitation practices, physical characteristics of the environment such as temperature and humidity, and modern shipping practices. Lymphatic filariasis, a mosquito-borne disease, has increased in frequency in parts of Africa in recent decades as a consequence of large-scale agricultural development projects that have shifted the nature and quantity of water sources and potential mosquito breeding sites. Dracunculiasis is transmitted by a small crustacean that contaminates sources of drinking water. Because its transmission can be prevented by a simple change in human behavior, filtering all water with a small piece of cloth before using it, dracunculiasis has been the focus of a major eradication effort that is near success.

Agriculture↗

PubMed2000

Bacterial pili: molecular mechanisms of pathogenesis.

Gram-negative bacteria produce a diverse array of pili that mediate microbe-microbe and host-pathogen interactions important in the development of disease. The structural and functional characterization of these organelles, particularly their role in triggering signals in both the bacterium and the host upon attachment, has begun to reveal the molecular mechanisms of bacterial diseases.

Animals↗

PubMed2005

Profiling early infection responses: Pseudomonas aeruginosa eludes host defenses by suppressing antimicrobial peptide gene expression.

Insights into the host factors and mechanisms mediating the primary host responses after pathogen presentation remain limited, due in part to the complexity and genetic intractability of host systems. Here, we employ the model Drosophila melanogaster to dissect and identify early host responses that function in the initiation and progression of Pseudomonas aeruginosa pathogenesis. First, we use immune potentiation and genetic studies to demonstrate that flies mount a heightened defense against the highly virulent P. aeruginosa strain PA14 when first inoculated with strain CF5, which is avirulent in flies; this effect is mediated via the Imd and Toll signaling pathways. Second, we use whole-genome expression profiling to assess and compare the Drosophila early defense responses triggered by the PA14 vs. CF5 strains to identify genes whose expression patterns are different in susceptible vs. resistant host-pathogen interactions, respectively. Our results identify pathogenesis- and defense-specific genes and uncover a previously undescribed mechanism used by P. aeruginosa in the initial stages of its host interaction: suppression of Drosophila defense responses by limiting antimicrobial peptide gene expression. These results provide insights into the genetic factors that mediate or restrict pathogenesis during the early stages of the bacterial-host interaction to advance our understanding of P. aeruginosa-human infections.

Animals↗

PubMed2006

Genomic approaches to understanding bacterial virulence.

The genomic sequences of bacterial pathogens and of the host species they infect have greatly increased the understanding of host-pathogen interactions. Sequences of bacterial genomes have led to the identification of virulence factors through the use of bioinformatics, targeted mutant library construction, screening approaches combining transposon mutagenesis and microarray technology, and through the expression of libraries of bacterial proteins within model organisms such as yeast. Host genomic information has also yielded insights into bacterial virulence through transcriptional profiling of host responses to infection and identification of host proteins required for bacterial pathogenicity using knockdown of host gene product expression during infection. Research using genomic approaches to bacterial pathogenesis is a rapidly growing field and will expand further as additional bacterial genome sequences become available and techniques for conducting high-throughput analysis are refined.

Bacteria↗

PubMed2005

Adherence molecules of pathogenic pneumococci.

Adherence molecules are key players in pathogen-host interactions. These are usually surface-exposed structures that facilitate adherence to host cells, or target host serum proteins of the extracellular matrix. Our knowledge of the function of pneumococcal cell-surface structures, and the basic mechanisms underlying their interaction with host receptor molecules has dramatically increased, through molecular and structural analysis of adherence molecules. In particular, choline-binding proteins have received considerable attention because of their versatility, and their sophisticated role in the interaction with host proteins. Interestingly, subversion of host-protein functions to facilitate host invasion and immune evasion has also been attributed to intracellular or surface-exposed proteins of the pathogen. Many of these molecules do not possess the classic features of bacterial surface proteins.

Adhesins, Bacterial↗

PubMed2004

Pine genes regulated by the necrotrophic pathogen Fusarium circinatum.

A targeted genomics approach was used to construct a cDNA array of potential pathogen-regulated genes for investigating host-pathogen interactions in pine trees (Pinus species). This array, containing a nonredundant set of 311 cDNAs, was assembled by combining smaller sets of cDNAs generated by differential display or suppression subtraction hybridization using a variety of pathogen treatments and elicitors. The array was probed to identify host genes regulated by Fusarium circinatum, a necrotrophic fungus that incited pitch canker disease on pine stems. A set of 29 cDNAs were induced during the disease state. Notably, cDNAs on the array that were derived from experiments with fusiform rust, incited by Cronartium quercuum f. sp. fusiforme (a biotrophic fungus) were unregulated by Fusarium. the results imply distinct genetic responses in pine to diseases incited by necrotrophs and biotrophs. This cDNA collection expands the genomics toolkit for understanding interactions between conifers and their microbial associates in forest ecosystems.

Base Sequence↗

PubMed1997

Host responses and antigens involved in protective immunity to Mycobacterium tuberculosis.

Tuberculosis (TB) is the largest single infectious cause of human mortality. The incidence of TB has remained high in most of the developing world and the disease has recently re-emerged as a public health problem in industrialized countries. The development of a new improved TB vaccine is a highly prioritized international research area, which has been further stimulated by the appearance of multi-drug resistant strains of Mycobacterium tuberculosis. The present status of the attempts to characterize the protective immune response to TB will be reviewed with special emphasis on recent progress in the identification and characterization of target molecules recognized by protective cells. This paper will focus on proteins released from live bacteria and discuss their role in the host-pathogen interaction and the ongoing attempts to use these molecules in TB subunit vaccines.

Antigen Presentation↗

PubMed2026

The Small Noncoding RNA, RsaC, Is Essential for Staphylococcus aureus Virulence.

BACKGROUND: Bacterial small noncoding RNAs (sRNAs) play critical roles in virulence, stress adaptation, and host-pathogen interactions. Transcriptomic analyses during infection can help reveal pathogen-derived sRNAs required for pathogenesis, providing valuable insights for the development of novel therapeutic strategies. However, the low abundance of pathogen biomass within the host tissues poses a significant challenge for such analyses. METHODS: We employed 2-step cell disruption to enrich Staphylococcus aureus cells from infected mouse organs and conducted RNA sequencing (RNA-seq) analysis to examine staphylococcal sRNAs expressed during infection. qRT-PCR was used to confirm the gene expression. A knockout mutant of highly expressed sRNA, RsaC, was generated, and RNA-seq under in vivo as well as in vitro aerobic and anaerobic conditions were compared between the wild-type and ΔrsaC strains. Virulence of S. aureus was assessed using both mouse and silkworm survival assays. RESULTS: We identified RsaC as one of the most highly expressed sRNAs in mouse organs with consistent increment over time postinfection. Through gene disruption and complementation, we demonstrated that RsaC is an independent virulence determinant required for full pathogenicity of S. aureus in a murine infection model. In addition, RsaC influenced gene expression in response to oxygen availability and host-associated stress. Further analysis revealed that mutation of 2 genes downregulated in ΔrsaC in vivo, NWMN_RS03420 (sodium: proton antiporter) and NWMN_RS12015 (hypothetical protein), reduced S. aureus virulence in a silkworm model. CONCLUSIONS: These findings identify RsaC as a novel independent virulence determinant that supports S. aureus adaptation within the host.

Animals↗

PubMed2026

Convergent evolution of immune evasion in ESKAPE pathogens: A cross-pathogen architecture of conserved host-defense checkpoints.

Antimicrobial resistance in ESKAPE pathogens is primarily attributed to resistance genes, yet persistent infections despite appropriate therapy implicate immune evasion as an independent driver of treatment failure. Although immune-evasion mechanisms have been extensively characterized in individual pathogens, their shared architecture across the ESKAPE group remains insufficiently integrated. This review synthesizes current evidence to show that phylogenetically diverse ESKAPE pathogens have convergently evolved conserved strategies to evade host immunity under comparable selective pressures. A cross-pathogen immune-evasion framework emerges, encompassing impaired pathogen recognition, complement inhibition, phagocyte dysfunction, immunometabolic reprogramming, biofilm-mediated protection, and persistence-promoting inflammation, together with pathogen-specific virulence mechanisms. These processes intersect with adaptive immune dysfunction and emerging concepts, including quorum-sensing-mediated immunomodulation, trained immunity, and the itaconate-succinate immunometabolic axis, forming an interconnected persistence network rather than isolated virulence traits. This systems-level perspective identifies conserved host-directed therapeutic targets that may complement conventional antimicrobial therapy across species. However, host-directed therapies, immunotherapeutics, and vaccines remain largely preclinical or have shown inconsistent clinical efficacy. Mechanistic evidence is strongest for Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, whereas substantial knowledge gaps persist for Enterococcus faecium, Acinetobacter baumannii, and Enterobacter spp. Overcoming persistent ESKAPE infections will require targeting conserved host-pathogen interactions alongside pathogen-specific antimicrobial resistance mechanisms.

Convergent immune evasion↗