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PubMed1998

"Black holes" and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli.

Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens. For example, Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensal Escherichia coli in the presence of a plasmid in Shigella that encodes virulence functions. However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is present in approximately 90% of E. coli strains but is uniformly absent in Shigella strains. When the gene for LDC, cadA, was introduced into Shigella flexneri 2a, virulence became attenuated, and enterotoxin activity was inhibited greatly. The enterotoxin inhibitor was identified as cadaverine, a product of the reaction catalyzed by LDC. Comparison of the S. flexneri 2a and laboratory E. coli K-12 genomes in the region of cadA revealed a large deletion in Shigella. Representative strains of Shigella spp. and enteroinvasive E. coli displayed similar deletions of cadA. Our results suggest that, as Shigella spp. evolved from E. coli to become pathogens, they not only acquired virulence genes on a plasmid but also shed genes via deletions. The formation of these "black holes," deletions of genes that are detrimental to a pathogenic lifestyle, provides an evolutionary pathway that enables a pathogen to enhance virulence. Furthermore, the demonstration that cadaverine can inhibit enterotoxin activity may lead to more general models about toxin activity or entry into cells and suggests an avenue for antitoxin therapy. Thus, understanding the role of black holes in pathogen evolution may yield clues to new treatments of infectious diseases.

Cadaverine↗

PubMed1997

A prospective study of the correlation between genital pathogens and morbidity following diathermy loop excision of the transformation zone.

A prospective study of 48 women was carried out to estimate the incidence of common genital pathogens in women referred to colposcopy clinic requiring diathermy loop excision and to compare patient morbidity in the subgroups with and without genital pathogens. Of the 43 women included in the analysis, genital pathogens were present in 24 cases (56%) and absent in 19 (44%) of the 24 positive cases, 19 (79%) women had pathogen(s) on the cervical swab, 24 (100%) had pathogen(s) on the high vaginal swab and 15 (63%) had both a positive cervical and high vaginal swab (HVS). The most frequently isolated groups of organisms were mixed anaerobes, alone (four HVS and four cervical) or in combination with Gardnerella vaginalis (four HVS and three cervical) or coliforms (two HVS and two cervical). The mean duration of bleeding and vaginal discharge in the two study groups was not statistically significant (t value 1.97, P 0.05; and t value 0.48, P 0.5, respectively). However, the mean duration of bleeding graded by the patient as being moderate to severe was significantly different in the two groups (t value 3.18 P 0.01). Fifty-six per cent of the women in the study had confirmed genital pathogens, predominantly anaerobes, and the prolonged moderate-to-severe bleeding in this group suggests a potential role for prophylactic bacteriocides, although the study size was unable to implicate a single pathogen.

Journal Article↗

PubMed2005

Challenges and opportunities for pathogen detection using DNA microarrays.

DNA microarrays offer the potential for simultaneous detection of many pathogens that are of interest to homeland security, public health, medicine, and veterinary diagnostics. These tools are best suited for detecting the presence or absence of genetic sequences characteristic of specific pathogens, but microarrays are poorly suited for determining pathogen viability, and current methods provide only limited potential for pathogen enumeration. Two basic strategies have been described for pathogen detection: using enzymatic amplification to generate targets for interrogation with a microarray, or using direct interrogation of DNA or RNA without pre-amplification. Multiplex PCR has the advantage of a high degree of sensitivity and specificity, but associated microarrays are necessarily limited in scope. PCR-independent, whole-genome amplification eliminates biases inherent in PCR amplification and can accommodate more extensive microarrays, but assay sensitivity is compromised and these methods are probably of limited use when testing tissue samples. Direct hybridization of DNA or RNA provides the least bias in gene detection, but also the lowest level of analytic sensitivity. Ultimately, cost and limited sample throughput make it unlikely that planar microarrays will play a significant role in future pathogen detection schemes. Alternative microarray formats such as bead arrays, however, may circumvent the cost and throughput limitations and permit us to apply what we have learned from planar microarrays to develop robust pathogen detection systems. Assay validation and sample preparation will continue to be significant challenges for these detection systems.

Animals↗

PubMed2005

Nitrogen metabolism of Aspergillus and its role in pathogenicity.

Aspergilli represent unique pathogens. Based on their saprophytic life style they are able to colonize a variety of ecological niches, among them the immunocompromised individual. Distinct fungal attributes that play a role in pathogenicity of aspergilli have been described, and primary metabolism indisputably has to be taken into account for contributing to the virulence potential of this fungal genus. Here we present an overview of studies that focus on this aspect of nutritional versatility. In the predominant pathogenic representative Aspergillus fumigatus regulation of nitrogen utilization and sensing of nitrogen sources have been scrutinized with respect to pathogenicity. The impact of distinct metabolic pathways on virulence capacities could be evaluated by inspection of auxotrophic mutant strains. Among them, para-aminobenzoic acid-requiring mutants revealed that this biosynthetic route is strictly required for pathogenicity. For amino acid anabolism only lysine biosynthesis has been investigated in this regard. Fungal amino acid biosynthesis is generally subject to strict regulation mediated by the Cross-Pathway Control system, a conserved regulatory circuit evolved to counteract conditions of nutritional stress. A clear influence of the system on pathogenicity could be observed by targeting its transcriptional activator CpcA. However, additional metabolic characteristics as well as regulatory instruments that compensate environmental challenges need to be addressed in future research with the aim to assess the significance of fungal primary metabolism for pathogenicity of aspergillus species.

Animals↗

PubMed1993

Nucleosome: a major immunogen for pathogenic autoantibody-inducing T cells of lupus.

Only a fraction (12%) of 268 "autoreactive" T cell clones derived from lupus-prone mice can selectively induce the production of pathogenic anti-DNA autoantibodies in vitro and accelerate the development of lupus nephritis when transferred in vivo. The CDR3 loops of T cell receptor beta chains expressed by these pathogenic T helper (Th) clones contain a recurrent motif of anionic residues suggesting that they are selected by autoantigens with cationic residues. Herein, we found that approximately 50% of these pathogenic Th clones were specific for nucleosomal antigens, but none of them responded to cationic idiopeptides shared by variable regions of pathogenic anti-DNA autoantibodies. Nucleosomes did not stimulate the T cells as a nonspecific mitogen or superantigen. Only the pathogenic Th cells of lupus responded to nucleosomal antigens that were processed and presented via the major histocompatibility class II pathway. Although the presentation of purified mononucleosomes to the Th clones could be blocked by inhibitors of endosomal proteases, neither of the two components of the nucleosomes--free DNA or histones by themselves--could stimulate the Th clones. Thus critical peptide epitopes for the Th cells were probably protected during uptake and processing of the nucleosome particle as a whole. The nucleosome-specific Th clones preferentially augmented the production of IgG autoantibodies to histone-DNA complex in vitro. In vivo, nucleosome-specific, CD4+ T cells were not detectable in normal mice, but they were found in the spleens of lupus-prone mice as early as 1 mo of age, long before other autoimmune manifestations. Immunization of young, preautoimmune lupus mice with nucleosomes augmented the production of autoantibodies and markedly accelerated the development of severe glomerulonephritis. Previously, crude preparations containing nucleosomes were shown by others to have polyclonal mitogenic activity for B cells from normal as well as lupus mice. Identification here of pure mononucleosome as a lupus-specific immunogen for the Th cells that selectively help the pathogenic anti-DNA autoantibody producing B cells of lupus could lead to the design of specific therapy against this pathogenic autoimmune response.

Amino Acid Sequence↗

PubMed2006

Host life-history strategy explains pathogen-induced sterility.

Virulence is often equated with pathogen-induced mortality, even though loss of fecundity is also common. But while the former may be understood as a simple consequence of lost host resources for the purposes of pathogen transmission, pathogen-induced sterility is often not associated with changes in host mortality. As a result, a separate literature has emerged to explain fecundity effects of parasitism that has not been integrated into general theories of the evolution of virulence. Here, I present a model of pathogen-induced sterility that is based on the assumption that hosts and pathogens vie for the same host resources for both reproduction and maintenance. Loss of host fecundity can then be explained by the host compensating for its future loss of resources, before infection. Such preinfection ;;fecundity compensation" may often cause preinfection investment in maintenance to be as low as postinfection levels, despite a loss of total host resources after infection. Thus, sterility is simply explained as a host life-history strategy in a system where the pathogen necessarily steals host resources for its own transmission. In certain circumstances, the pathogen may even be able to manipulate the host to redirect resources away from reproduction and toward maintenance through castration, causing gigantism.

Animals↗

PubMed2006

Annual Medicago: from a model crop challenged by a spectrum of necrotrophic pathogens to a model plant to explore the nature of disease resistance.

BACKGROUND: Annual Medicago spp., including M. truncatula, play an important agronomic role in dryland farming regions of the world where they are often an integral component of cropping systems, particularly in regions with a Mediterranean or Mediterranean-type climate where they grow as winter annuals that provide both nitrogen and disease breaks for rotational crops. Necrotrophic foliar and soil-borne pathogens dominate these regions and challenge the productivity of annual Medicago and crop legume species. SCOPE: This review outlines some of the major and/or widespread diseases these necrotrophic pathogens cause on Medicago spp. It then explores the potential for using the spectrum of necrotrophic pathogen-host interactions, with annual Medicago as the host plant, to better understand and model pathosystems within the diseases caused by nectrotrophic pathogens across forage and grain legume crops. CONCLUSIONS: Host resistance clearly offers the best strategy for cost-effective, long-term control of necrotrophic foliar and soil-borne pathogens, particularly as useful resistance to a number of these diseases has been identified. Recently and initially, the annual M. truncatula has emerged as a more appropriate and agronomically relevant substitute to Arabidopsis thaliana as a model plant for legumes, and is proving an excellent model to understand the mechanisms of resistance both to individual pathogens and more generally to most forage and grain legume necrotrophic pathogens.

Medicago↗

PubMed2001

Activity of telithromycin, a new ketolide antibacterial, against atypical and intracellular respiratory tract pathogens.

Atypical respiratory pathogens such as Mycoplasma pneumoniae and intracellular pathogens such as Legionella spp. and Chlamydia spp. form a significant proportion of the aetiological agents underlying community-acquired pneumonia (CAP). The clinical signs or radiological features of atypical pneumonia are generally insufficient to predict accurately the pathogen involved; in addition, high costs and a considerable length of time are involved in the identification of atypical pathogens. Treatment is, therefore, most often empirical, and it is important that the activity of antibacterial agents available to treat CAP is sufficiently broad to eradicate infection with both common and atypical bacterial pathogens. Telithromycin (HMR 3647) is the first of a new family of antibacterials, the ketolides, and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs). The excellent activity of telithromycin against the respiratory tract bacterial pathogens most commonly associated with community-acquired RTIs, including resistant strains, is well established. This review examines the considerable body of evidence showing that telithromycin also has a high level of activity against atypical and intracellular respiratory tract bacterial pathogens.

Anti-Bacterial Agents↗

PubMed2006

PHI-base: a new database for pathogen host interactions.

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/.

Algal Proteins↗

PubMed2005

Defense-related genes expressed in Norway spruce roots after infection with the root rot pathogen Ceratobasidium bicorne (anamorph: Rhizoctonia sp.).

To study the mechanisms of inducible disease resistance in conifers, changes in transcript accumulation in roots of Norway spruce (Picea abies (L.) Karst.) seedlings exposed to the root rot pathogen Ceratobasidium bicorne Erikss. and Ryv. (anamorph: Rhizoctonia sp.) were monitored by differential display (DD). Because C. bicorne attacks root tips, a desiccation treatment was added to exclude genes induced by pathogen-related desiccation stress. The DD analysis was defined by the use of 11 sets of primers, covering about 5% of the transcriptome. A comparison of gene expression in control, desiccation- and pathogen-stressed roots revealed 36 pathogen-induced gene transcripts. Based on database searches, these transcripts were assigned to four groups originating from spruce mRNA (25 transcripts), rRNA (five transcripts), fungal mRNA (two transcripts) and currently unknown cDNAs (four transcripts). Real-time PCR was applied to verify and quantify pathogen-induced changes in transcript accumulation. Of the 18 transcripts tested, nine were verified to be Norway spruce gene transcripts up-regulated from 1.3- to 66-fold in the infected roots. Four germin-like protein isoforms, a peroxidase and a glutathione S-transferase, all implicated in oxidative processes, including the oxidative burst, were predicted from sequence similarity searches. Seven class IV chitinase isoforms implicated in fungal cell wall degradation and a nucleotide binding site-leucine rich repeat (NBS-LRR) disease resistance protein homologue related to pathogen recognition were identified. Several transcript species, such as the NBS-LRR homologue and the germin-like protein homologues, have not previously been identified as pathogen-inducible genes in gymnosperms.

Amino Acid Sequence↗

PubMed2006

Uncommon respiratory pathogens.

PURPOSE OF REVIEW: In many cases, the specific pathogen responsible for a respiratory infection is not identified and can lead to improper medical treatment, increased duration of illness, and possibly contributes to the development of antibiotic resistance. Molecular-based diagnostic methodologies have significantly improved our ability to identify common respiratory pathogens; these techniques are not useful, however, when a novel pathogen is responsible for the infection and clinicians must rely on differential diagnosis for the treatment of patients. RECENT FINDINGS: New pathogens previously not associated with human infections have been identified in the past few years. In addition, new strains of bacteria and viruses have emerged as the causative agents of pneumonia and acute respiratory distress. Protozoans and saprophytic fungi, which are not normally associated with respiratory infection, have also emerged as respiratory pathogens particularly in individuals with AIDS or in those who are otherwise immunocompromised. SUMMARY: This review discusses the recent literature on newly described respiratory pathogens as well as opportunistic pathogens that can infect the respiratory system of immunocompromised individuals. The studies referenced here reveal the need for expanded laboratory tests and highly trained microbiologists in clinical laboratories worldwide.

Animals↗

PubMed2001

Weeding and grooming of pathogens in agriculture by ants.

The ancient mutualism between fungus-growing ants and the fungi they cultivate for food is a textbook example of symbiosis. Fungus-growing ants' ability to cultivate fungi depends on protection of the garden from the aggressive microbes associated with the substrate added to the garden as well as from the specialized virulent garden parasite Escovopsis. We examined ants' ability to remove alien microbes physically by infecting Atta colombica gardens with the generalist pathogen Trichoderma viride and the specialist pathogen Escovopsis. The ants sanitized the garden using two main behaviours: grooming of alien spores from the garden (fungus grooming) and removal of infected garden substrate (weeding). Unlike previously described hygienic behaviours (e.g. licking and self-grooming), fungus-grooming and garden-removal behaviours are specific responses to the presence of fungal pathogens. In the presence of pathogens, they are the primary activities performed by workers, but they are uncommon in uninfected gardens. In fact, workers rapidly eliminate Trichoderma from their gardens by fungus grooming and weeding, suggesting that these behaviours are the primary method of garden defence against generalist pathogens. The same sanitary behaviours were performed in response to the presence of the specialist pathogen Escovopsis. However, the intensity and duration of these behaviours were much greater in this treatment. Despite the increased effort, the ants were unable to eliminate Escovopsis from their gardens, suggesting that this specialized pathogen has evolved counter-adaptations in order to overcome the sanitary defences of the ants.

Animals↗

PubMed2005

Rapid detection of food-borne pathogens by using molecular techniques.

Traditional methods of identification of food-borne pathogens, which cause disease in humans, are time-consuming and laborious, so there is a need for the development of innovative methods for the rapid identification of food-borne pathogens. Recent advances in molecular cloning and recombinant DNA techniques have revolutionized the detection of pathogens in foods. In this study the development of a PCR-based technique for the rapid identification of the food-borne pathogens Salmonella and Escherichia coli was undertaken. Suitable primers were designed based on specific gene fimA of Salmonella and gene afa of pathogenic E. coli for amplification. Agarose gel electrophoresis and subsequent staining with ethidium bromide were used for the identification of PCR products. The size of the amplified product was 120 bp as shown by comparison with marker DNA. These studies have established that fimA and afa primers were specific for detecting Salmonella and pathogenic E. coli, respectively, in the environmental samples. Thus a rapid, sensitive and reliable technique for the detection of Salmonella and pathogenic E. coli was developed.

Adhesins, Escherichia coli↗

PubMed2005

Systemic acquired tolerance to virulent bacterial pathogens in tomato.

Recent studies on the interactions between plants and pathogenic microorganisms indicate that the processes of disease symptom development and pathogen growth can be uncoupled. Thus, in many instances, the symptoms associated with disease represent an active host response to the presence of a pathogen. These host responses are frequently mediated by phytohormones. For example, ethylene and salicylic acid (SA) mediate symptom development but do not influence bacterial growth in the interaction between tomato (Lycopersicon esculentum) and virulent Xanthomonas campestris pv vesicatoria (Xcv). It is not apparent why extensive tissue death is integral to a defense response if it does not have the effect of limiting pathogen proliferation. One possible function for this hormone-mediated response is to induce a systemic defense response. We therefore assessed the systemic responses of tomato to Xcv. SA- and ethylene-deficient transgenic lines were used to investigate the roles of these phytohormones in systemic signaling. Virulent and avirulent Xcv did induce a systemic response as evidenced by expression of defense-associated pathogenesis-related genes in an ethylene- and SA-dependent manner. This systemic response reduced cell death but not bacterial growth during subsequent challenge with virulent Xcv. This systemic acquired tolerance (SAT) consists of reduced tissue damage in response to secondary challenge with a virulent pathogen with no effect upon pathogen growth. SAT was associated with a rapid ethylene and pathogenesis-related gene induction upon challenge. SAT was also induced by infection with Pseudomonas syringae pv tomato. These data show that SAT resembles systemic acquired resistance without inhibition of pathogen growth.

Bacteria↗

PubMed2005

An Arabidopsis homeodomain transcription factor, OVEREXPRESSOR OF CATIONIC PEROXIDASE 3, mediates resistance to infection by necrotrophic pathogens.

The mechanisms controlling plant resistance to necrotrophic fungal pathogens are poorly understood. We previously reported on Ep5C, a gene shown to be induced by the H(2)O(2) generated during a plant-pathogen interaction. To identify novel plant components operating in pathogen-induced signaling cascades, we initiated a large-scale screen using Arabidopsis thaliana plants carrying the beta-glucuronidase reporter gene under control of the H(2)O(2)-responsive Ep5C promoter. Here, we report the identification and characterization of a mutant, ocp3 (for overexpressor of cationic peroxidase 3), in which the reporter construct is constitutively expressed. Healthy ocp3 plants show increased accumulation of H(2)O(2) and express constitutively the Glutathione S-transferase1 and Plant Defensine 1.2 marker genes, but not the salicylic acid (SA)-dependent pathogenesis-related PR-1 gene. Strikingly, the ocp3 mutant shows enhanced resistance to the necrotrophic pathogens Botrytis cinerea and Plectosphaerella cucumerina. Conversely, resistance to virulent forms of the biotrophic oomycete Hyaloperonospora parasitica and the bacterial pathogen Pseudomonas syringae pv tomato DC3000 remains unaffected in ocp3 plants when compared with wild-type plants. Consistently with this, ocp3 plants are not affected in SA perception and express normal levels of PR genes after pathogen attack. To analyze signal transduction pathways where ocp3 operates, epistasis analyses between ocp3 and pad4, nahG, npr1, ein2, jin1, or coi1 were performed. These studies revealed that the resistance signaling to necrotrophic infection in ocp3 is fully dependent on appropriate perception of jasmonic acid through COI1 and does not require SA or ethylene perception through NPR1 or EIN2, respectively. The OCP3 gene encodes a homeodomain transcription factor that is constitutively expressed in healthy plants but repressed in response to infection by necrotrophic fungi. Together, these results suggest that OCP3 is an important factor for the COI1-dependent resistance of plants to infection by necrotrophic pathogens.

Arabidopsis↗

PubMed2006

Physical and functional interactions between pathogen-induced Arabidopsis WRKY18, WRKY40, and WRKY60 transcription factors.

Limited information is available about the roles of specific WRKY transcription factors in plant defense. We report physical and functional interactions between structurally related and pathogen-induced WRKY18, WRKY40, and WRKY60 transcription factors in Arabidopsis thaliana. The three WRKY proteins formed both homocomplexes and heterocomplexes and DNA binding activities were significantly shifted depending on which WRKY proteins were present in these complexes. Single WRKY mutants exhibited no or small alterations in response to the hemibiotrophic bacterial pathogen Pseudomonas syringae and the necrotrophic fungal pathogen Botrytis cinerea. However, wrky18 wrky40 and wrky18 wrky60 double mutants and the wrky18 wrky40 wrky60 triple mutant were substantially more resistant to P. syringae but more susceptible to B. cinerea than wild-type plants. Thus, the three WRKY proteins have partially redundant roles in plant responses to the two distinct types of pathogens, with WRKY18 playing a more important role than the other two. The contrasting responses of these WRKY mutants to the two pathogens correlated with opposite effects on pathogen-induced expression of salicylic acid-regulated PATHOGENESIS-RELATED1 and jasmonic acid-regulated PDF1.2. While constitutive expression of WRKY18 enhanced resistance to P. syringae, its coexpression with WRKY40 or WRKY60 made plants more susceptible to both P. syringae and B. cinerea. These results indicate that the three WRKY proteins interact both physically and functionally in a complex pattern of overlapping, antagonistic, and distinct roles in plant responses to different types of microbial pathogens.

Amino Acid Motifs↗

PubMed2001

Patterns of association between crucifers and their flower-mimic pathogens: host jumps are more common than coevolution or cospeciation.

Morphological and molecular phylogenies of animal parasites have often shown parallel cladogenesis, supporting hypotheses of coevolution. Few studies of the phylogenetic history for plants and their pathogens exist. Gene-for-gene interactions suggest that plant pathogens ought to have similar phylogenetic histories as their hosts. However, high dispersability combined with an inability to choose to leave if an inappropriate host has been landed on could increase the likelihood of host jumps and thus decrease phylogenetic congruence between plant pathogens and their hosts. In this study, I examined the pattern of association between the flower-mimicking crucifer rusts and their hosts by comparing independent host phylogenies (based on both cpDNA trnL-F introns and nuclear internal transcribed spacer [ITS] sequences) with that of their rust pathogens (based on ITS sequences). The expectation was that if the pathogens coevolved or cospeciated with their hosts, then their phylogenies should be congruent. Host-tracking coevolution can be differentiated from cospeciation by examining the times of divergence: If the pathogens are younger than the hosts, then it is likely that host tracking has occurred. For the crucifer rusts and their hosts, there was little evidence of parallel cladogenesis, suggesting that both cospeciation and coevolutionary tracking are rare. Instead, the most common pattern was one of host jumps to geographically associated taxa. There are at least three factors that may have contributed to the geographic structuring of the data. First, along the east-west transect stretching from the Rocky Mountains to California, large differences in rainfall and the timing of rainfall may reduce long-distance gene flow. Second, although dispersal of infectious spores is by wind, sexual reproduction of these fungi depends on insects, which move short distances. Third, host shifts are most likely to occur to geographically available taxa. Any species that grows adjacent to infected plants will be exposed to millions of spores, and the probability of eventual infection by a new mutant increases with greater exposure. Thus, patterns of association between the crucifers and their flower-mimic pathogens reflect jumps to geographically available hosts, which are not necessarily those that are most closely related.

Brassicaceae↗

PubMed2004

Down-regulation of pathogenic autoantibody response in a slowly progressive Heymann nephritis kidney disease model.

In the present article, we describe an antigen-specific down-regulation of a pathogenic autoantibody (aab)-mediated disease process in an experimental autoimmune kidney disease in rats called slowly progressive Heymann nephritis (SPHN). This autoimmune disease is initiated and maintained by pathogenic immunoglobulin G (IgG) autoantibodies (aabs), which cause an immune-complex (IC) glomerulonephritis associated with proteinuria. We achieved down-regulated pathogenic aab response in SPHN rats by injections of an IC containing the native nephritogenic antigen and specific high-titred nonpathogenic IgM aabs, in antigen excess. The injected IC increased the level of circulating nonpathogenic IgM aabs; the increased levels of specific IgM aabs in turn facilitated the removal of the injected altered nephritogenic and liberated autoantigens from the renal tubules and greatly diminished the production of pathogenic aabs and the build up of immune deposits in the glomeruli. While animals treated early had advantages over rats whose kidney disease was well established before treatment; animals treated late into the disease still manifested noticeable improvements in similar areas, i.e. with lessened proteinuria, kidney lesion reduction and a decreased pathogenic aab response. At the end of the experiment at 29 weeks, 80% of all the treated rats had insignificantly low levels of circulating IgG aabs, indicating cessation of pathogenic aab production and corresponding termination of the disease process. In contrast, most untreated rats with the kidney disease still had high levels of circulating pathogenic aabs at the end of the experiment, which maintained disease progression.

Animals↗