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As in other bacterial pathogens, the virulence determinants of Listeria species are clustered in genomic islands scattered along the chromosome. This review summarizes current knowledge about the structure, distribution and role in pathogenesis of Listeria virulence loci. Hypotheses about the mode of acquisition and evolution of these loci in this group of Gram-positive bacteria are presented and discussed.
A cDNA clone (RaRO47) encoding a sulfotransferase (ST) has been isolated from Arabidopsis cell suspensions. The deduced polypeptide of 302 amino acids is highly related to plant flavonol sulfotransferases (FSTs), characterized for the first time in Flaveria, and also to STs from animal tissue. The expression of the Arabidopsis ST gene(s) corresponding to RaR047 was examined during different developmental stages. It was found that, at the level of steady-state mRNA, expression of gene(s) encoding this ST was rapidly induced in the aerial parts of young seedlings, and during growth of Arabidopsis cell cultures. No expression could be detected in roots. Treatment of Arabidopsis seedlings with hormonal or stress-related compounds, showed that RaR047 mRNA accumulation was more particularly induced in response to salicylic acid and methyl jasmonate. Furthermore, in the leaves of mature plants or in cell suspensions, accumulation of RaR047 mRNA was observed upon infection with bacterial pathogens. This expression was observed preferentially in response to avirulent pathogens causing an hypersensitive reaction, as compared to virulent pathogens, which lead to disease.
The Xylella fastidiosa genome program generated a large number of gene sequences that belong to pathogenicity, virulence and adaptation categories from this important plant pathogen. One of these genes (XF1729) encodes a protein similar to a superfamily of aldo-keto reductase together with a number of structurally and functionally related NADPH-dependent oxidoreductases. In this work, the similar sequence XF1729 from X. fastidiosa was cloned onto the pET32Xa/LIC vector in order to overexpress a recombinant His-tag fusion protein in Escherichia coli BL21(DE3). The expressed protein in the soluble fraction was purified by immobilized metal affinity chromatography (agarose-IDA-Ni resin). Secondary structure contents were verified by circular dichroism spectroscopy. Small angle X-ray scattering (SAXS) measurements furnish general structural parameters and provide a strong indication that the protein has a monomeric form in solution. Also, ab initio calculations show that the protein has some similarities with a previously crystallized aldo-keto reductase protein. The recombinant XF1729 purified to homogeneity catalyzed the reduction of dl-glyceraldehyde (K(cat) 2.26s(-1), Km 8.20+/-0.98 mM) and 2-nitrobenzaldehyde (K(cat) 11.74 s(-1), Km 0.14+/-0.04 mM) in the presence of NADPH. The amino acid sequence deduced from XF1729 showed the highest identity (40% or higher) with several functional unknown proteins. Among the identified AKRs, we found approximately 29% of identity with YakC (AKR13), 30 and 28% with AKR11A and AKR11B, respectively. The results establish XF1729 as the new member of AKR family, AKR13B1. Finally, the first characterization by gel filtration chromatography assays indicates that the protein has an elongated shape, which generates an apparent higher molecular weight. The study of this protein is an effort to fight X. fastidiosa, which causes tremendous losses in many economically important plants.
Fungal pathogens possess virulence factors that allow them to cause disease in humans and animals. Combinations of properties such as temperature tolerance, evasion of host defences, dimorphism, and enzymatic activities may serve as virulence mechanisms for fungi.
Systemic pathogens have developed numerous strategies for evading the defenses of the host, permitting dissemination and multiplication in various tissues. One means of survival in the host, particularly in the bloodstream, has been attributed to the ability to avoid phagocytosis via capsular polysaccharide. To further define the virulence capacity of Streptococcus iniae, a zoonotic pathogen with the ability to cause severe systemic disease in both fish and humans, we performed an analysis of the capsule locus. The initial analysis included cloning and sequencing of the capsule synthesis operon, which revealed an approximately 21-kb region that is highly homologous to capsule operons of other streptococci. A genetic comparison of S. iniae virulent strain 9117 and commensal strain 9066 revealed that the commensal strain does not have the central region of the capsule operon composed of several important capsule synthesis genes. Four 9117 insertion or deletion mutants with mutations in the beginning, middle, or end of the capsule locus were analyzed to determine their capsule production and virulence. Virulence profiles were analyzed for each mutant using three separate criteria, which demonstrated the attenuation of each mutant in several tissue environments. These analyses also provided insight into the different responses of the host to each mutant strain compared to a wild-type infection. Our results demonstrate that capsule is not required for all host environments, while excess capsule is also not optimal, suggesting that for an "ideal" systemic infection, capsule production is most likely regulated while the bacterium is in different environments of the host.
To utilize effectively the growing number of verified genes that mediate an organism's ability to cause disease and/or to trigger host responses, we have developed PHI-base. This is a web-accessible database that currently catalogs 405 experimentally verified pathogenicity, virulence and effector genes from 54 fungal and Oomycete pathogens, of which 176 are from animal pathogens, 227 from plant pathogens and 3 from pathogens with a fungal host. PHI-base is the first on-line resource devoted to the identification and presentation of information on fungal and Oomycete pathogenicity genes and their host interactions. As such, PHI-base is a valuable resource for the discovery of candidate targets in medically and agronomically important fungal and Oomycete pathogens for intervention with synthetic chemistries and natural products. Each entry in PHI-base is curated by domain experts and supported by strong experimental evidence (gene/transcript disruption experiments) as well as literature references in which the experiments are described. Each gene in PHI-base is presented with its nucleotide and deduced amino acid sequence as well as a detailed description of the predicted protein's function during the host infection process. To facilitate data interoperability, we have annotated genes using controlled vocabularies (Gene Ontology terms, Enzyme Commission Numbers and so on), and provide links to other external data sources (e.g. NCBI taxonomy and EMBL). We welcome new data for inclusion in PHI-base, which is freely accessed at www4.rothamsted.bbsrc.ac.uk/phibase/.
In the present review article, recent molecular advances relating to studies with Taylorella equigenitalis, as well as the recently described second species of the genus Taylorella, namely Taylorella asinigenitalis, have been described. Molecular genotyping of T. equigenitalis strains by pulsed-field gel electrophoresis (PFGE) after digestion with the suitable restriction enzyme(s) enabled the effective discrimination of strains, thus allowing the examination of the scientific mechanism(s) for its occurrence and transmission of contagious equine metritis (CEM). Alternatively, polymerase chain reaction (PCR) amplification and nucleotide sequencing of the 16S ribosomal DNA sequence and/or the other species specific sequence(s) as targets were confirmed to be effective for identification of T. equigenitalis. These new analytical methods at the genomic DNA level also enabled the discrimination of the newly discovered donkey-related T. asinigenitalis from T. equigenitalis, and moreover, the performance of phylogenetic analysis of genus Taylorella organisms with other closely related genera. Furthermore, detailed analysis of the genes responsible for CEM within the T. equigenitalis genome would be useful to help elucidate the pathogenic virulence and transmission mechanisms associated with the important equine pathogen associated with CEM.
Plant innate immunity against invasive biotrophic pathogens depends on the intracellular defense regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). We show here that Arabidopsis thaliana EDS1 interacts in vivo with another protein, SENESCENCE-ASSOCIATED GENE101 (SAG101), discovered through a proteomic approach to identify new EDS1 pathway components. Together with PHYTOALEXIN-DEFICIENT4 (PAD4), a known EDS1 interactor, SAG101 contributes intrinsic and indispensable signaling activity to EDS1-dependent resistance. The combined activities of SAG101 and PAD4 are necessary for programmed cell death triggered by the Toll-Interleukin-1 Receptor type of nucleotide binding/leucine-rich repeat immune receptor in response to avirulent pathogen isolates and in restricting the growth of normally virulent pathogens. We further demonstrate by a combination of cell fractionation, coimmunoprecipitation, and fluorescence resonance energy transfer experiments the existence of an EDS1-SAG101 complex inside the nucleus that is molecularly and spatially distinct from EDS1-PAD4 associations in the nucleus and cytoplasm. By contrast, EDS1 homomeric interactions were detected in the cytoplasm but not inside the nucleus. These data, combined with evidence for coregulation between individual EDS1 complexes, suggest that dynamic interactions of EDS1 and its signaling partners in multiple cell compartments are important for plant defense signal relay.
Control of emerging infectious diseases will be difficult because of the large number of disease-causing organisms that are emerging or could emerge and the great diversity of geographic areas in which emergence can occur. The modern view of the evolution of pathogen virulence--specifically its focus on the tradeoff between costs and benefits to the pathogen from increased host exploitation--allows control programs to identify and focus on the most dangerous pathogens (those that can be established with high virulence in human populations).
Ethylene evolution occurs concomitantly with the progression of disease symptoms in response to many virulent pathogen infections in plants. A tomato mutant impaired in ethylene perception-Never ripe-exhibited a significant reduction in disease symptoms in comparison to the wild type after inoculations of both genotypes with virulent bacterial (Xanthomonas campestris pv vesicatoria and Pseudomonas syringae pv tomato) and fungal (Fusarium oxysporum f sp lycopersici) pathogens. Bacterial spot disease symptoms were also reduced in tomato genotypes impaired in ethylene synthesis (1-aminocyclopropane-1-carboxylic acid deaminase) and perception (14893), thereby corroborating a reducing effect for ethylene insensitivity on foliar disease development. The reduction in foliar disease symptoms in Never ripe plants was a specific effect of ethylene insensitivity and was not due to reductions in bacterial populations or decreased ethylene synthesis. PR-1B1 mRNA accumulation in response to X. c. vesicatoria infection was not affected by ethylene insensitivity, indicating that ethylene is not required for defense gene induction. Our findings suggest that broad tolerance of diverse vegetative diseases may be achieved via engineering of ethylene insensitivity in tomato.
Virulence for bean and soybean is determined by effector genes in a plasmid-borne pathogenicity island (PAI) in race 7 strain 1449B of Pseudomonas syringae pv. phaseolicola. One of the effector genes, avrPphF, confers either pathogenicity, virulence, or avirulence depending on the plant host and is absent from races 2, 3, 4, 6, and 8 of this pathogen. Analysis of cosmid clones and comparison of DNA sequences showed that the absence of avrPphF from strain 1448A is due to deletion of a continuous 9.5-kb fragment. The remainder of the PAI is well conserved in strains 1448A and 1449B. The left junction of the deleted region consists of a chimeric transposable element generated from the fusion of homologs of IS1492 from Pseudomonas putida and IS1090 from Ralstonia eutropha. The borders of the deletion were conserved in 66 P. syringae pv. phaseolicola strains isolated in different countries and representing the five races lacking avrPphF. However, six strains isolated in Spain had a 10.5-kb deletion that extended 1 kb further from the right junction. The perfect conservation of the 28-nucleotide right repeat of the IS1090 homolog in the two deletion types and in the other 47 insertions of the IS1090 homolog in the 1448A genome strongly suggests that the avrPphF deletions were mediated by the activity of the chimeric mobile element. Our data strongly support a clonal origin for the races of P. syringae pv. phaseolicola lacking avrPphF.
Plant natural resistance to potential parasites is regulated by two fundamental mechanisms: the "nonhost" and the "gene-for-gene" resistance, respectively. The latter is relevant when a cultivar resistant (R) gene product recognizes an avirulence gene product in the attacking pathogen and triggers an array of biochemical reactions that halt the pathogen around the site of attempted invasion. To cope with virulent pathogens, plants may benefit by some temporary immunity after a challenge triggering such an array of defense reactions, following a localized necrotizing infection as a possible consequence of a hypersensitive response (HR). This process, mediated by accumulation of endogenous salicylic acid (SA), is called systemic acquired resistance (SAR) and provides resistance, to a certain extent even against unrelated pathogens, such as viruses, bacteria, and fungi, for a relatively long-lasting period. SAR may be more potently activated in plants pretreated with chemical inducers, most of which appear to act as functional analogues of SA. This review summarizes the complex aspects of SAR as a way to prevent crop diseases by activating the plants' own natural defenses. The following outline is taken: (1) introduction through the historical insight of the phenomenon; (2) oxidative burst, which produces high levels of oxygen reactive species in a way similar to the inflammation state in animals and precedes the HR to the pathogen attack; (3) SAR as a coordinate action of several gene products leading to the expression of defenses well beyond the time and space limits of the HR; (4) jasmonic acid (JA) and ethylene as other endogenous factors mediating a different pathway of induced resistance; (5) pathogenesis related proteins (PR proteins) de novo synthesized as specific markers of SAR; (6) exogenous inducers of SAR, which include both synthetic chemicals and natural products; (7) the pathway of signal transduction between sensitization by inducers and PR expression, as inferred by mutageneses, a process that is still, to a large extent, not completely elucidated; (8) prospects and costs; (9) final remarks on the state-of-the-art of the topic reflecting the chemical view of the author, based on the more authoritative ones expressed by the authors of the reviewed papers.
In this paper, the author constructs a general, continuous-time dynamical model of a coevolutionary host-microparasite interaction, which incorporates host resistance (degree of susceptibility to invasion by the parasite) and parasite virulence (pathogenicity and transmission efficiency). Discrete classes of resistance type and virulence type are allowed. It is assumed that high virulence parasite strains are able to take over hosts already occupied by lower virulence strains. Heritability of host resistance is assumed, but specific assumptions about the genetics of such inheritance are avoided. Instead, a 'neutral' view is adopted, which assumes that the disease process is the sole selective force acting on a disease-free resistance distribution. This allows the dimensionality of the model to be kept lower than corresponding explicitly population-genetic models. Ecological factors are taken into account via density dependence in host encounter rate (which also influences transmission properties of the disease via contact transmission), and by density dependence in host fecundity. Two distinct host types are considered, which we call 'bunchers' and 'separators', characterized by the form of reaction of the encounter rate to changes in host density. Detailed analyses are given for versions of the model having: (a) one resistance class and one virulence class; (b) two resistance classes and one virulence class; (c) two resistance classes and two virulence classes. Sufficient conditions are found in case (c) for the low resistance type to be eliminated by the coevolutionary process. Features which might tend to promote resistance polymorphism are also discussed.
Despite impressive advances in the study of plant resistance to pathogens, little is known about the molecular basis of plant susceptibility to virulent pathogens. Recent progress in susceptible plant-Pseudomonas syringae interactions has provided a glimpse into the battles fought between plants and bacterial pathogens. A key step for pathogenesis appears to be the suppression of host defenses. Suppression of host defenses, including basal defense, gene-for-gene resistance and nonhost resistance, is a key step for pathogenesis. Defense suppression is mediated by bacterial effector proteins, which are secreted through the type III secretion system, and by coronatine, a bacterial toxin that structurally and functionally mimics methyl jasmonate, a plant defense signaling molecule.
We describe the characterization of a novel gain-of-function Arabidopsis mutant, dll1 (disease-like lesions1), which spontaneously develops lesions mimicking bacterial speck disease and constitutively expresses biochemical and molecular markers associated with pathogen infection. Despite the constitutive expression of defense-related responses, dll1 is unable to suppress the growth of virulent pathogens. However, dll1 elicits normal hypersensitive response in response to avirulent pathogens, thus indicating that dll1 is not defective in the induction of normal resistance responses. The lesion+ leaves of dll1 support the growth of hrcC mutant of Pseudomonas syringae, which is defective in the transfer of virulence factors into the plant cells, and therefore non-pathogenic to wild-type Col-0 plants. This suggests that dll1 intrinsically expresses many of the cellular processes that are required for pathogen growth during disease. Epistasis analyses reveal that salicylic acid and NPR1 are required for lesion formation, while ethylene modulates lesion development in dll1, suggesting that significant overlap exist between the signalling pathways leading to resistance- and disease-associated cell death. Our results suggest that host cell death during compatible interactions, at least in part, is genetically controlled by the plant and DLL1 may positively regulate this process.
Environmental pathogenic fungi present a paradox in that they are virulent in animals without requiring animal hosts for replication or survival, a phenomenon we call 'ready-made' virulence. In the human pathogenic fungus Cryptococcus neoformans, the capacity for virulence in animals may originate from environmental selective pressures imposed by such organisms as amoeboid and nematode predators. Many C. neoformans virulence factors appear to have 'dual use' capabilities that confer survival advantages in both animal hosts and in the environment. The findings with C. neoformans may provide a paradigm for understanding the origin and maintenance of virulence in other pathogenic environmental fungi.
In this study Vibrio proteolyticus CW8T2 has been identified as a virulent pathogen for Artemia spp. Its infection route has been visualized with transmission electron microscopy. The pathogen affected microvilli and gut epithelial cells, disrupted epithelial cell junctions, and reached the body cavity, where it devastated cells and tissues. In vivo antagonism tests showed that preemptive colonization of the culture water with nine selected bacterial strains protected Artemia juveniles against the pathogenic effects. Two categories of the selected strains could be distinguished: (i) strains providing total protection, as no mortality occurred 2 days after the experimental infection with V. proteolyticus CW8T2, with strain LVS8 as a representative, and (ii) strains providing partial protection, as significant but not total mortality was observed, with strain LVS2 as a representative. The growth of V. proteolyticus CW8T2 in the culture medium was slowed down in the presence of strains LVS2 and LVS8, but growth suppression was distinctly higher with LVS8 than with LVS2. It was striking that the strains that gave only partial protection against the pathogen in the in vivo antagonism test showed also a restricted capability to colonize the Artemia compared to the strains providing total protection. The in vivo antagonism tests and the filtrate experiments showed that probably no extracellular bacterial compounds were involved in the protective action but that the living cells were required to protect Artemia against V. proteolyticus CW8T2.
Many pathogenic microbes have multiple virulence factors that can cause damage to the host and thus contribute to an overall virulence phenotype for that organism. Although current techniques are suitable for demonstrating that a particular microbial characteristic contributes to virulence, no formal approach for defining the relative contributions of multiple virulence factors to overall virulence has been proposed. This paper describes the use of multivariate linear regression to estimate the relative contributions of virulence factors to the overall phenomenon of virulence. The approach is illustrated here with sample calculations of the relative contributions of individual Cryptococcus neoformans and Bacillus anthracis virulence factors to the overall virulence phenotype. These calculations were derived from a small underpowered experimental data set for the fungus and two larger sets of randomly generated data for both microbes. The major limitation of this method is a requirement for large data sets of microbial strains that differ in virulence and virulence factor expression. Multivariate linear regression can be used to identify the relative levels of importance of virulence factors in virulence studies, and this information can be used to prioritize antigen identification for vaccine development and the design of antimicrobial strategies that target virulence mechanisms.