Model For Host-pathogen Interactions Research Articles

Iron Acquisition Strategies of Vibrio anguillarum.

The hemorrhagic septicemic disease vibriosis caused by Vibrio anguillarum shows noticeable similarities to invasive septicemia in humans, and in this case, the V. anguillarum–host system has the potential to serve as a model for understanding native eukaryotic host–pathogen interactions. Iron acquisition, as a fierce battle occurring between pathogenic V. anguillarum and the fish host, is a pivotal step for virulence. In this article, advances in defining the roles of iron uptake pathways in growth and virulence of V. anguillarum have been summarized, divided into five aspects, including siderophore biosynthesis and secretion, iron uptake, iron release, and regulation of iron uptake. Understanding the molecular mechanisms of iron acquisition will have important implications for the pathogenicity of this organism.

Immune Receptors and Co-receptors in Antiviral Innate Immunity in Plants.

Plants respond to pathogens using an innate immune system that is broadly divided into PTI (pathogen-associated molecular pattern- or PAMP-triggered immunity) and ETI (effector-triggered immunity). PTI is activated upon perception of PAMPs, conserved motifs derived from pathogens, by surface membrane-anchored pattern recognition receptors (PRRs). To overcome this first line of defense, pathogens release into plant cells effectors that inhibit PTI and activate effector-triggered susceptibility (ETS). Counteracting this virulence strategy, plant cells synthesize intracellular resistance (R) proteins, which specifically recognize pathogen effectors or avirulence (Avr) factors and activate ETI. These coevolving pathogen virulence strategies and plant resistance mechanisms illustrate evolutionary arms race between pathogen and host, which is integrated into the zigzag model of plant innate immunity. Although antiviral immune concepts have been initially excluded from the zigzag model, recent studies have provided several lines of evidence substantiating the notion that plants deploy the innate immune system to fight viruses in a manner similar to that used for non-viral pathogens. First, most R proteins against viruses so far characterized share structural similarity with antibacterial and antifungal R gene products and elicit typical ETI-based immune responses. Second, virus-derived PAMPs may activate PTI-like responses through immune co-receptors of plant PTI. Finally, and even more compelling, a viral Avr factor that triggers ETI in resistant genotypes has recently been shown to act as a suppressor of PTI, integrating plant viruses into the co-evolutionary model of host-pathogen interactions, the zigzag model. In this review, we summarize these important progresses, focusing on the potential significance of antiviral immune receptors and co-receptors in plant antiviral innate immunity. In light of the innate immune system, we also discuss a newly uncovered layer of antiviral defense that is specific to plant DNA viruses and relies on transmembrane receptor-mediated translational suppression for defense.

Relevant Genes Linked to Virulence Are Required for Salmonella Typhimurium to Survive Intracellularly in the Social Amoeba Dictyostelium discoideum.

The social amoeba Dictyostelium discoideum has proven to be a useful model for studying relevant aspects of the host-pathogen interaction. In this work, D. discoideum was used as a model to study the ability of Salmonella Typhimurium to survive in amoebae and to evaluate the contribution of selected genes in this process. To do this, we performed infection assays using axenic cultures of D. discoideum co-cultured with wild-type S. Typhimurium and/or defined mutant strains. Our results confirmed that wild-type S. Typhimurium is able to survive intracellularly in D. discoideum. In contrast, mutants ΔaroA and ΔwaaL are defective in intracellular survival in this amoeba. Next, we included in our study a group of mutants in genes directly linked to Salmonella virulence. Of note, mutants ΔinvA, ΔssaD, ΔclpV, and ΔphoPQ also showed an impaired ability to survive intracellularly in D. discoideum. This indicates that S. Typhimurium requires a functional biosynthetic pathway of aromatic compounds, a lipopolysaccharide containing a complete O-antigen, the type III secretion systems (T3SS) encoded in SPI-1 and SPI-2, the type VI secretion system (T6SS) encoded in SPI-6 and PhoP/PhoQ two-component system to survive in D. discoideum. To our knowledge, this is the first report on the requirement of O-antigen and T6SS in the survival of Salmonella within amoebae. In addition, mutants ΔinvA and ΔssaD were internalized in higher numbers than the wild-type strain during competitive infections, suggesting that S. Typhimurium requires the T3SS encoded in SPI-1 and SPI-2 to evade phagocytosis by D. discoideum. Altogether, these results indicate that S. Typhimurium exploits a common set of genes and molecular mechanisms to survive within amoeba and animal host cells. The use of D. discoideum as a model for host–pathogen interactions will allow us to discover the gene repertoire used by Salmonella to survive inside the amoeba and to study the cellular processes that are affected during infection.

A hypothetical model of host-pathogen interaction of Streptococcus suis in the gastro-intestinal tract

ABSTRACTStreptococcus suis (SS) is a zoonotic pathogen that can cause systemic infection in pigs and humans. The ingestion of contaminated pig meat is a well-established risk factor for zoonotic S. suis disease. In our studies, we provide experimental evidence that S. suis is capable to translocate across the host gastro-intestinal tract (GIT) using in vivo and in vitro models. Hence, S. suis should be considered an emerging foodborne pathogen. In this addendum, we give an overview of the complex interactions between S. suis and host-intestinal mucosa which depends on the host origin, the serotype and genotype of S. suis, as well as the presence and expression of virulence factors involved in host-pathogen interaction. Finally, we propose a hypothetical model of S. suis interaction with the host-GIT taking in account differences in conditions between the porcine and human host.

Screening, isolation and optimization of anti–white spot syndrome virus drug derived from terrestrial plants

To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various terrestrial plants and to evaluate the efficacy of the same in host-pathogen interaction model. Thirty plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. The best anti-WSSV plant isolate, TP22C was isolated and further analyzed. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug. Seven plant isolates exhibited significant survivability in host. The drug TP22C thus formulated showed 86% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of TP22C required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 750 mg/kg body weight/day survived at the rate of 86%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection. The drug TP22C derived from Momordica charantia is a potent anti-white spot syndrome virus drug.

Screening, isolation and optimization of anti–white spot syndrome virus drug derived from marine plants

To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various marine floral ecosystems and to evaluate the efficacy of the same in host-pathogen interaction model. Thirty species of marine plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. By means of chemical processes, the purified anti-WSSV plant isolate, MP07X was derived. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug. Nine plant isolates exhibited significant survivability in host. The drug MP07X thus formulated showing 85% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of MP07X required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 1 000 mg/kg body weight/day survived at the rate of 85%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection. The drug MP07X derived from Rhizophora mucronata is a potent anti-WSSV drug.

Survival of taylorellae in the environmental amoeba Acanthamoeba castellanii

BackgroundTaylorella equigenitalis is the causative agent of contagious equine metritis, a sexually-transmitted infection of Equidae characterised in infected mares by abundant mucopurulent vaginal discharge and a variable degree of vaginitis, cervicitis or endometritis, usually resulting in temporary infertility. The second species of the Taylorella genus, Taylorella asinigenitalis, is considered non-pathogenic, although mares experimentally infected with this bacterium can develop clinical signs of endometritis. To date, little is understood about the basic molecular virulence and persistence mechanisms employed by the Taylorella species. To clarify these points, we investigated whether the host-pathogen interaction model Acanthamoeba castellanii was a suitable model for studying taylorellae.ResultsWe herein demonstrate that both species of the Taylorella genus are internalised by a mechanism involving the phagocytic capacity of the amoeba and are able to survive for at least one week inside the amoeba. During this one-week incubation period, taylorellae concentrations remain strikingly constant and no overt toxicity to amoeba cells was observed.ConclusionsThis study provides the first evidence of the capacity of taylorellae to survive in a natural environment other than the mammalian genital tract, and shows that the alternative infection model, A. castellanii, constitutes a relevant alternative system to assess host-pathogen interactions of taylorellae. The survival of taylorellae inside the potential environmental reservoir A. castellanii brings new insight, fostering a broader understanding of taylorellae biology and its potential natural ecological niche.

3: Integrin-linked kinase modulates LPS-induced TNFα production via regulation of p65 phosphorylation at serine 536 during NF-kB activation

Integrin-Linked Kinase (ILK) is a ubiquitously expressed protein that regulates cell responses to a wide variety of extracellular stimuli, however its role in the innate immune system is largely unknown. We have studied its role in mediating pro-inflammatory signalling in response to LPS. Pharmacologic or genetic inhibition of ILK in MEFS and macrophages selectively blocks LPS-induced production of the pro-inflammatory cytokine TNF-α. Our results have shown that ILK is required for TLR-induced NF-κB activation and transcriptional induction of TNF-α, through an ILK-PI3K axis. We have demonstrated that the modulation of LPS-induced TNF-α synthesis by ILK does not involve the classical NF-κB pathway since IkBα degradation and p65 nuclear translocation are both unaffected by ILK inhibition. Instead, ILK is involved in a non-classical activation of NF-κB signalling by modulating the phosphorylation of p65 at ser536. Furthermore, ILK-mediated non-classical NF-κB activation through p65 ser536 phosphorylation also exists in a host-pathogen interaction model using Helicobacter pyroli infection in macrophages and gastric cancer cells. Our findings implicate ILK as a critical regulatory molecule for NF-κB- mediated proinflammatory signalling pathway, which is vital for innate immune responses against pathogenic microorganisms.

Current trends in modeling host–pathogen interactions

AbstractThe rapid emergence of infectious diseases calls for immediate attention to determine practical solutions for intervention strategies. To this end, it becomes necessary to obtain a holistic view of the complex host–pathogen interactome. Advances in omics and related technology have resulted in massive generation of data for the interacting systems at unprecedented levels of detail. Systems‐level studies with the aid of mathematical tools contribute to a deeper understanding of biological systems, where intuitive reasoning alone does not suffice. In this review, we discuss different aspects of host–pathogen interactions (HPIs) and the available data resources and tools used to study them. We discuss in detail models of HPIs at various levels of abstraction, along with their applications and limitations. We also enlist a few case studies, which incorporate different modeling approaches, providing significant insights into disease. © 2013 Wiley Periodicals, Inc.This article is categorized under: Algorithmic Development > Biological Data Mining

Extinction of Disease Pathogenesis in Infected Population and Its Subsequent Recovery: A Stochastic Approach

A stochastic mathematical model of host-pathogen interaction has been developed to estimate the time to extinction of infected population. It has been assumed in the model that the infected host does not grow or reproduce but can recover from pathogenic infection and move to add to the susceptible host population using various drugs or vaccination. Extinction of infected population in host-pathogen interaction depends significantly upon the total population. Here, we consider an extension of our previous work with the stochastic approach to predict the time to extinction of disease pathogenesis. The optimal control approach helped in designing an innovative, safe therapeutic regimen where the susceptible host population enhanced with simultaneous decrease in the infected population. By means of an optimal control theory paradigm, it has also been shown in our preceding research paper that the cost-effective combination of treatment may depend on the population size. In this research paper, we have studied an approximation which is derived in favor of quasi-stationary distribution along with the expected time to extinction for the model of host-pathogen interactions. The complete study has been roofed through the stochastic approach in context that disease pathogenesis is to be extinct and infected population are going to be recovered. Numerical simulation is also done to confirm the analysis.

Role of SPI-1 secreted effectors in acute bovine response to Salmonella enterica Serovar Typhimurium: a systems biology analysis approach.

Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis with diarrhea and polymorphonuclear cell (PMN) influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS) encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrhea-associated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT) and a ΔsipA, sopABDE2 mutant (MUT) across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic Bayesian network modeling approach (DBN). Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-β, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host-pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response at early time points of infection (15 minutes, 30 minutes and one hour) within phosphatidylinositol, CCR3, Wnt, and TGF-β signaling pathways and the regulation of actin cytoskeleton pathway.

Experimental Tuberculosis in the Wistar Rat: A Model for Protective Immunity and Control of Infection

BackgroundDespite the availability of many animal models for tuberculosis (TB) research, there still exists a need for better understanding of the quiescent stage of disease observed in many humans. Here, we explored the use of the Wistar rat model for the study of protective immunity and control of Mycobacterium tuberculosis (Mtb) infection.Methodology/Principal FindingsThe kinetics of bacillary growth, evaluated by the colony stimulating assay (CFU) and the extent of lung pathology in Mtb infected Wistar rats were dependent on the virulence of the strains and the size of the infecting inoculums. Bacillary growth control was associated with induction of T helper type 1 (Th1) activation, the magnitude of which was also Mtb strain and dose dependent. Histopathology analysis of the infected lungs demonstrated the formation of well organized granulomas comprising epithelioid cells, multinucleated giant cells and foamy macrophages surrounded by large numbers of lymphocytes. The late stage subclinical form of disease was reactivated by immunosuppression leading to increased lung CFU.ConclusionThe Wistar rat is a valuable model for better understanding host-pathogen interactions that result in control of Mtb infection and potentially establishment of latent TB. These properties together with the ease of manipulation, relatively low cost and well established use of rats in toxicology and pharmacokinetic analyses make the rat a good animal model for TB drug discovery.

Extracellular Paracoccidioides brasiliensis phospholipase B involvement in alveolar macrophage interaction

BackgroundPhospholipase B (PLB) has been reported to be one of the virulence factors for human pathogenic fungi and has also been described as necessary for the early events in infection. Based on these data, we investigated the role of PLB in virulence and modulation of the alveolar pulmonary immune response during infection using an in-vitro model of host-pathogen interaction, i.e. Paracoccidioides brasiliensis yeast cells infecting alveolar macrophage (MH-S) cells.ResultsThe effect of PLB was analyzed using the specific inhibitor alexidine dihydrochloride (0.25 μM), and pulmonary surfactant (100 μg mL-1), during 6 hours of co-cultivation of P. brasiliensis and MH-S cells. Alexidine dihydrochloride inhibited PLB activity by 66% and significantly decreased the adhesion and internalization of yeast cells by MH-S cells. Genes involved in phagocytosis (trl2, cd14) and the inflammatory response (nfkb, tnf-α, il-1β) were down-regulated in the presence of this PLB inhibitor. In contrast, PLB activity and internalization of yeast cells significantly increased in the presence of pulmonary surfactant; under this condition, genes such as clec2 and the pro-inflammatory inhibitor (nkrf) were up-regulated. Also, the pulmonary surfactant did not alter cytokine production, while alexidine dihydrochloride decreased the levels of interleukin-10 (IL-10) and increased the levels of IL-12 and tumor necrosis factor-α (TNF-α). In addition, gene expression analysis of plb1, sod3 and icl1 suggests that P. brasiliensis gene re-programming is effective in facilitating adaptation to this inhospitable environment, which mimics the lung-environment interaction.ConclusionP. brasiliensis PLB activity is involved in the process of adhesion and internalization of yeast cells at the MH-S cell surface and may enhance virulence and subsequent down-regulation of macrophage activation.

Stochastic Spatial Models of Host-Pathogen and Host-Mutualist Interactions II

Plant community structure is shaped by interactions among plants and their pathogens and mutualists (collectively called symbionts). Some symbionts are highly specialized, others are generalists, adding to the complexity of interactions. The development of a conceptual framework that is based on idealized models is a necessary step in reaching a level of understanding that would allow us to predict outcomes of these interactions. In this paper, we introduce spatially explicit, stochastic models of multispecies host-symbionts interactions with a specific focus on how the degree of specialization affects coexistence of multiple hosts and their symbionts, and, in case of coexistence, what spatial patterns result. Our rigorous results, supplemented by simulations, give a complete description of the behavior of these host-symbionts models. It is proved analytically that generalist symbionts have only a limited effect on the structure of host communities which, in contrast, can be significantly altered by specialist mutualists, with the most beneficial mutualist together with its most preferred hosts outcompeting all the other species. Numerical simulations further suggest that, in the neutral case, specialist pathogens promote the local diversity whereas specialist mutualists lead to a coarse-grained habitat. This paper also contains conjectures for future research directions.

Three-Dimensional Visualization of Immunological Processes of Entire Organs in Subcellular Resolution.

Abstract 61In vivo models of complex immune processes like stem cell engraftment, host-pathogen interactions or anti-tumor responses face the challenge to either provide dynamic information in low resolution (e.g. in vivo bioluminescence Imaging, BLI) or provide high resolution information with a limited field of view (e.g. multi-photon laser scanning microscopy/confocal microscopy).To overcome these limitations we applied a novel selective plane illumination microscopy (SPIM) technique (also termed ultramicroscopy), which enabled us to visualize structural and cellular changes in intact organs in high resolution. Here we investigated dynamic shifts at sites of graft-versus-host disease (GVHD) initiation in mice after allogenic hematopoietic cell transplantation (allo-HCT).For in vivo and ex vivo imaging we transplanted 1,2×106 luciferase+ DsRed+ transgenic C57Bl/6 T cells (H-2b, Thy1.1+) plus 5×106 bone marrow (BM) cells (H-2b, Thy1.2+) into myeloablative conditioned allogeneic Balb/c recipients (H-2d, Thy1.2+, 8 Gy) to induce aGVHD. Utilizing BLI we followed the development of GVHD in vivo. At the transition from GVHD initiation phase to effector phase (day+3 and day+4) we prepared the small bowel and Peyer‘s Patches (PPs) of allo-HCT recipients for whole organ microscopy and compared these to organs of untreated mice.Staining for T cell populations (CD4) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) allowed us to visualize MAdCAM-1 expression in relation to T cell areas in whole PPs and surrounding intestinal mucosa (> 8mm3) in a high throughput format by creating approx. 1000 optical sections using multiple lasers and a sensitive CCD camera within 10 minutes. Adding another color channel revealed structural details through measurement of intrinsic autofluorescence. The individual color stacks were overlaid via computational image processing for three dimensional tissue reconstruction, volume measurements and quantification of protein expression.Ultramicroscopy exposed microanatomical structures like intestinal villi, crypts and PPs with its subepithelial dome regions and follicles by giving detailed information about MAdCAM-1 expressing blood vessels and T cell areas. The 3D reconstruction of small intestines in non-conditioned mice revealed that the MAdCAM-1 expression averaged at 1-2% of the entire PP and was predominantly restricted to the high endothelial venules (HEV). During the transition from the initiation to the effector phase of acute GVHD (day3-4) the overall MAdCAM-1 expression in PPs increased by 50fold. At this point MAdCAM-1 expression was also found in parafollicular and subepithelial cell populations, which still need to be characterized further concerning their lineage differentiation.MAdCAM-1 is well known as a vascular addressin molecule. Because of its importance in homing of α4β7+ T and B cell into the gastrointestinal tract we investigated the dynamic expression of MAdCAM-1 during acute GVHD within intact PPs. It is well established that MAdCAM-1 is an important regulator in the homing of α4β7+ T cell to PPs via HEVs. Additionally our data lead to the hypothesis that MAdCAM-1 might contribute to retain proliferating α4β7+ T cells during the initiation of an adaptive immune response and might support a synchronized exit of alloreactive T cells in the aGVHD effector phase.Conventional histological sections are labor intensive, time consuming and often restricted to a very limited region of interest and therefore, can result in missing rare events and under- or overestimation of biological processes. Ultramicroscopy helped us to overcome these limitations and enabled us to visualize immunological processes with subcellular resolution in whole organs.CB and MF, GSH and AB contributed equally to this work. Disclosures:No relevant conflicts of interest to declare.

Rho GTPase-activating bacterial toxins: from bacterial virulence regulation to eukaryotic cell biology

Studies on the interactions of bacterial pathogens with their host have provided an invaluable source of information on the major functions of eukaryotic and prokaryotic cell biology. In addition, this expanding field of research, known as cellular microbiology, has revealed fascinating examples of trans-kingdom functional interplay. Bacterial factors actually exploit eukaryotic cell machineries using refined molecular strategies to promote invasion and proliferation within their host. Here, we review a family of bacterial toxins that modulate their activity in eukaryotic cells by activating Rho GTPases and exploiting the ubiquitin/proteasome machineries. This family, found in human and animal pathogenic Gram-negative bacteria, encompasses the cytotoxic necrotizing factors (CNFs) from Escherichia coli and Yersinia species as well as dermonecrotic toxins from Bordetella species. We survey the genetics, biochemistry, molecular and cellular biology of these bacterial factors from the standpoint of the CNF1 toxin, the paradigm of Rho GTPase-activating toxins produced by urinary tract infections causing pathogenic Escherichia coli. Because it reveals important connections between bacterial invasion and the host inflammatory response, the mode of action of CNF1 and its related Rho GTPase-targetting toxins addresses major issues of basic and medical research and constitutes a privileged experimental model for host-pathogen interaction.

Fitness consequences of infection of Arabidopsis thaliana with its natural bacterial pathogen Pseudomonas viridiflava

Variation in plant resistance to pathogen infection is commonly observed in interactions between wild plants and their foliar pathogens. Models of host-pathogen interactions indicate that a large cost of infection is generally necessary to maintain this variation, yet there is limited evidence that foliar pathogens cause detectable fitness reductions in wild host plants. Most published work has focused on fungal pathogens. Pseudomonas viridiflava, a common bacterial pathogen of the annual weed Arabidopsis thaliana across its range, comprises two distinct genetic clades that cause disease symptoms of different severity. Here we measured the extent of infection of wild A. thaliana populations in the Midwest, USA, and examined the effect on seed production, in field and growth-chamber experiments, of experimental inoculation with isolates from the two clades. We found infection with P. viridiflava varied from 0 to 56% in Midwest A. thaliana populations, with the possibility of several leaves per plant infected later in the growing season. In the growth chambers, experimental inoculation reduced seed set by averages of 15 and 11% for clades A and B, respectively. In the field experiment, only clade A affected plant fitness significantly, reducing seed set by an average of 38%. Underlying these average effects we observed both negative and positive effects of infection, and variation in both fitness among plant genotypes and sensitivity to environmental conditions.

Stochastic spatial models of host-pathogen and host-mutualist interactions I

Mutualists and pathogens, collectively called symbionts, are ubiquitous in plant communities. While some symbionts are highly host-specific, others associate with multiple hosts. The outcomes of multispecies host-symbiont interactions with different degrees of specificity are difficult to predict at this point due to a lack of a general conceptual framework. Complicating our predictive power is the fact that plant populations are spatially explicit, and we know from past research that explicit space can profoundly alter plant-plant interactions. We introduce a spatially explicit, stochastic model to investigate the role of explicit space and host-specificity in multispecies host-symbiont interactions. We find that in our model, pathogens can significantly alter the spatial structure of plant communities, promoting coexistence, whereas mutualists appear to have only a limited effect. Effects are more pronounced the more host-specific symbionts are.

Transmission rates and adaptive evolution of pathogens in sympatric heterogeneous plant populations.

Diversification in agricultural cropping patterns is widely practised to delay the build-up of virulent races that can overcome host resistance in pathogen populations. This can lead to balanced polymorphism, but the long-term consequences of this strategy for the evolution of crop pathogen populations are still unclear. The widespread occurrence of sibling species and reproductively isolated sub-species among fungal and oomycete plant pathogens suggests that evolutionary divergence is common. This paper develops a mathematical model of host-pathogen interactions using a simple framework of two hosts to analyse the influences of sympatric host heterogeneity on the long-term evolutionary behaviour of plant pathogens. Using adaptive dynamics, which assumes that sequential mutations induce small changes in pathogen fitness, we show that evolutionary outcomes strongly depend on the shape of the trade-off curve between pathogen transmission on sympatric hosts. In particular, we determine the conditions under which the evolutionary branching of a monomorphic into a dimorphic population occurs, as well as the conditions that lead to the evolution of specialist (single host range) or generalist (multiple host range) pathogen populations.

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.