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Results for “Pathogen diversity”

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PubMed2006

Host mediated selection of pathogen genotypes as a mechanism for the maintenance of baculovirus diversity in the field.

The genetic diversity of many DNA virus populations in nature is unknown, but for those that have been studied it has been found to be relatively high. This is particularly true for baculoviruses, a family of large double-stranded DNA viruses that infect the larval stages of insects. Why there should be such heterogeneity within these virus populations is puzzling and what sustains it is still unknown. It has long been recognized that some baculoviruses have a relatively wide host range, but the effect of different host species on the genotypic structure of a baculovirus population has received little attention. We provide evidence that infection of different insect species can influence the genetic diversity of a Panolis flammea nucleopolyhedrovirus (PaflNPV) population, isolated from the pine beauty moth. Variable regions of the PaflNPV genome were sequenced and novel ORFs were identified on each of the enlarged fragments. The roles of these orfs and the implications of their presence or absence within different genotypes are discussed. The variable fragments were also labelled with 32P and used as polymorphic genetic markers of genotype abundance. The proportion of polymorphic loci changed after passage in different insect species and this varied among species, suggesting a role for host selection of pathogen genotypes in the field as a mechanism for maintaining genetic diversity. These results have wide-ranging implications for understanding the ecology of insect-virus interactions in the natural environment and the evolution of baculovirus life history strategies.

Animals↗

PubMed2006

Regulatory RNAs as mediators of virulence gene expression in bacteria.

Bacteria exploit functional diversity of RNAs in a wide range of regulatory mechanisms to control gene expression. In last few years, small RNA molecules have been discovered at a staggering rate in bacteria, mainly in Escherichia coli. While functions of many of these RNA molecules are still not known, several of them behave as key effectors of adaptive responses, such as environmental cue recognition, stress response, and virulence control. Most fascinating, perhaps, is the discovery that mRNAs behave as direct sensors of small molecules or of environmental cues. The astonishing diversity of RNA-dependent regulatory mechanisms is linked to the dynamic properties and versatility of the RNA structure. In this review, we relate several recent studies in different bacterial pathogens that illustrate the diverse roles of RNA to control virulence gene expression.

Bacteria↗

PubMed2004

The many important facets of T-cell repertoire diversity.

In the thymus, a diverse and polymorphic T-cell repertoire is generated by random recombination of discrete T-cell receptor (TCR)-alphabeta gene segments. This repertoire is then shaped by intrathymic selection events to generate a peripheral T-cell pool of self-MHC restricted, non-autoaggressive T cells. It has long been postulated that some optimal level of TCR diversity allows efficient protection against pathogens. This article focuses on several recent advances that address the required diversity for the generation of an optimal immune response.

Animals↗

PubMed1994

Genetic heterogeneity in five captive specific pathogen-free groups of rhesus macaques.

Gene diversity was used to estimate genetic heterogeneity in the founders of five specific pathogen-free (SPF) colonies of rhesus macaques (Macaca mulatta) and ranged from about 0.20 to 0.32. In the founders of three groups at the California Regional Primate Research Center (CRPRC) that have been minimally managed to maintain genetic heterogeneity, gene diversity was about 0.30, approximately the value for that species, and has declined at the rate of only about 2.5% per generation since 1976. Without intervention, less than half the gene diversity in SPF harem groups will remain after 5 generations whereas gene diversity in multimale SPF groups should decline at less than half that rate. The proportion of gene diversity attributable to average differences among the three groups at the CRPRC, indicating the level of genetic subdivision, was lower than that in the founders of all but one of the SPF colonies and actually declined slightly over a 10-year period. Genetic subdivision in SPF colonies consisting of harem breeding groups was about three times that in colonies consisting of multimale breeding groups. The number of male breeders should be increased and variance in male reproductive success should be reduced in all SPF colonies, especially those containing multimale breeding groups. Genetic heterogeneity can most easily be retained, and genetic subdivision prevented, in each breeding group in all SPF colonies by ensuring gene flow among the breeding groups in each colony. Male breeders who exceed the lowest acceptable level of reproductive success in their colony of origin should also be exchanged among different SPF colonies to maximize the effective population size of the breeding groups in all SPF colonies.

Animals↗

PubMed2004

The changing field of vaccine development in the genomics era.

An improved understanding of the human immune system and the genetic make-up of pathogens, together with advances in instrumentation and bioinformatics, have provided new insights into the variation of immune responses to vaccines within the human population. Pathogen variation and the diversity of the immune system components within the human population make the design of universal vaccines difficult. New subunit vaccines that target immunologically similar subgroups of the human population and representative pathogen variants are emerging from research that combines immunomics, pathogen genomics, and high-throughput instrumentation.

Genome, Human↗

PubMed1998

Comparison of Randomly Amplified Polymorphic DNA with Amplified Fragment Length Polymorphism To Assess Genetic Diversity and Genetic Relatedness within Genospecies III of Pseudomonas syringae.

Recently, DNA pairing analyses showed that Pseudomonas syringae pv. tomato and related pathovars, including P. syringae pv. maculicola, form a genomic species (Pseudomonas tomato) (L. Gardan, H. L. Shafik, and P. A. D. Grimont, p. 445-448, in K. Rudolph, T. J. Burr, J. W. Mansfield, D. Stead, A. Vivian, and J. von Kietzell, ed., Pseudomonas syringae Pathovars and Related Pathogens, 1997). The genetic diversity of 23 strains belonging to this genomic species and 4 outgroup strains was analyzed with randomly amplified polymorphic DNA (RAPD) and amplified fragment length polymorphic (AFLP) techniques. Simple boiling of P. syringae cells was suitable for subsequent DNA amplification to obtain reliable patterns in RAPD and AFLP analyses. In general, the grouping of P. syringae strains by both analysis techniques corresponded well with the classification obtained from an RFLP analysis of ribosomal DNA operons, DNA pairing studies, and an analysis of pathogenicity data. However, two strains of P. syringae pv. maculicola produced distinct DNA patterns compared to the DNA patterns of other P. syringae pv. maculicola strains; these patterns led us to assume that horizontal transfer of DNA could occur between bacterial populations. Both techniques used in this study have high discriminating power because strains of P. syringae pv. tomato and P. syringae pv. maculicola which were indistinguishable by other techniques, including pathogenicity tests on tomato, were separated into two groups by both RAPD and AFLP analyses. In addition, data analysis showed that the AFLP method was more efficient for assessing intrapathovar diversity than RAPD analysis and allowed clear delineation between intraspecific and interspecific genetic distances, suggesting that it could be an alternative to DNA pairing studies. However, it was not possible to distinguish the two races of P. syringae pv. tomato on the basis of an analysis of the data provided by either the AFLP or RAPD technique.

Journal Article↗

PubMed2002

Correlation between variation of the 3' region of the cagA gene in Helicobacter pylori and disease outcome in Japan.

Genetic diversity within the cag pathogenicity island (PAI) of Helicobacter pylori may have a modifying effect on the pathogenic potential of the infecting strain. The genetic structure of the cag PAI was examined in Japanese isolates. The composition and nucleotide sequences of the cag PAI were quite similar among strains; however, diversity between 2 cag genes (virB10 and cagA) was observed. The variety in the number of repetition of the 5-amino acid sequence R1 (EPIYA) in the 3' region of the cagA gene was identified. The frequencies of the genotypes that contained >4 R1 sequences were significantly higher in atrophic gastritis-causing strains than in duodenal ulcer-causing strains. One-third of strains with >4 R1 sequences were gastric cancer-causing strains. Although the cag PAI is conserved in H. pylori isolates in Japan, H. pylori infection with the cagA genotype with >4 R1 sequences may correlate with the pathogenesis of atrophic gastritis and gastric cancer.

Amino Acid Sequence↗

PubMed2000

Genetic diversity of Porphyromonas gingivalis and its possible importance to pathogenicity.

During recent years much effort has been put into understanding the genetic composition of the oral populations of black-pigmented anaerobic bacteria. One of them, Porphyromonas gingivalis, is a putative periodontopathogenic organism considered to be particularly relevant in the etiology of adult periodontitis. It has been shown in studies using molecular typing methods that most bacterial populations consist of numerous genetic clones, and that only a small proportion of these clones cause disease. Elucidation of a possible association of genotypic profiles with either disease or clinical healthy condition is important for understanding the pathogenic characteristics of bacteria. Studies addressing this issue as it relates to P. gingivalis are reviewed in the present article. Genotypic characterization of P. gingivalis strains has revealed extensive heterogeneity in natural populations of this bacterium. Some of the potential virulence factors of P. gingivalis have been purified and cloned and methods have been established to identify their genes. Although no studies have clearly defined the relationship between a specific genotype of P. gingivalis and periodontal status of the host, it seems that molecular typing tools, which are undergoing rapid improvements, will allow us to distinguish between virulent and avirulent strains of the same species in the near future.

Adult↗

PubMed1991

[Isolation of enteropathogenic microorganism from patients with infection of the digestive tract during 1976 to 1988 in Tenri Hospital].

Enteropathogenic microorganisms isolated from feces of 9,393 patients with diarrhea or enteritis in our hospital between 1976 and 1988 were analyzed. As the result of the examination of 5,443 outpatients, 1,811 strains of pathogens were isolated from 1,686 cases (31.0%). Several species including Salmonella spp., Escherichia coli serotype, Vibrio parahaemolyticus, were isolated before 1978, and the incidence of pathogens was low (14.8%). For the 10-year period since 1979, the incidence markedly increased to 34.4%, and the number of pathogens isolated also increased to about twice that before 1978. The main cause of the increase was Campylobacter species. The major pathogens detected since 1979 were Campylobacter spp., E. coli serotype, Salmonella spp., V. parahaemolyticus, etc., but Rota virus, Clostridium difficile, Aeromonas spp., Vibrio fluvialis, etc. have also been detected, showing an increase in the number and diversity of the detected pathogens. As the result of the examination of 3,950 inpatients, 835 strains of pathogens were isolated from 800 cases (20.3%). The incidence of C. difficile was the highest, 423 of 800, followed by E. coli serotype, Salmonella spp., Campylobacter spp., V. parahaemolyticus and Aeromonas spp., in that order. All the inpatients from whom C. difficile was isolated manifested diarrhea or enteritis after administration of antimicrobial agents. The pathogens causing communicable disease were Salmonella spp. serovar Typhi, Salmonella spp. serovar Paratyphi A, Shigella flexneri, Shigella sonnei and Entamoeba histolytica, which were isolated from 5, 1, 3, 2 and inpatients, respectively.

Adolescent↗

PubMed2026

Clinical impact of metagenomic next-generation sequencing for pathogen identification and guided therapy in pediatric intensive care unit patients with severe pulmonary infections.

UNLABELLED: To explore the diagnostic efficiency, clinical concordance, and precision treatment value of metagenomic next-generation sequencing (mNGS) for severe pulmonary infections in children in the pediatric intensive care unit (PICU), and to provide evidence for improving microbiological diagnosis and optimizing anti-infective strategies. A retrospective cohort study included 89 children with severe pneumonia in the PICU in 2024. All underwent routine microbiological testing and mNGS of bronchoalveolar lavage fluid (BALF). Detection rates, pathogen composition, co-infection identification, diagnostic concordance, and treatment impact were analyzed. Metagenomic next-generation sequencing demonstrated high diagnostic sensitivity in the PICU setting, achieving a positive detection rate of 90.0% (80/89) and identifying a diverse spectrum of 103 pathogens, including 50.5% viruses, 43.7% bacteria, 38.8% co-infections (vs 11.6%), and 86.3% diagnostic concordance (vs 55.8%, P < 0.01). Among 46 patients included in the therapeutic outcome analysis (22 in the mNGS-guided group), 21 patients in the mNGS-guided group improved. Multivariate logistic regression analysis, adjusting for confounding factors (age, underlying diseases, PaO2/FiO2 ratio, PRISM III score, and preoperative antibiotic use duration), confirmed that mNGS-guided therapy was an independent protective factor for achieving the primary outcome (OR = 5.23, 95% CI: 1.87-14.61, P = 0.002) and secondary outcomes (C-reactive protein reduction ≥50%: OR = 4.89, 95% CI: 1.72-13.93, P = 0.003; oxygenation improvement: OR = 5.67, 95% CI: 1.98-16.21, P = 0.001). Metagenomic next-generation sequencing demonstrated high diagnostic sensitivity in the PICU setting, guiding precision therapy, and improving prognosis. IMPORTANCE: It supports metagenomic next-generation sequencing (mNGS) as a supplementary tool for pediatric intensive care unit (PICU) refractory infections, guides anti-infective adjustments, and informs tiered diagnostic pathways for resource-limited settings to optimize cost-effectiveness.

Humans↗

PubMed1999

Identification of an ancestral resistance gene cluster involved in the coevolution process between Phaseolus vulgaris and its fungal pathogen Colletotrichum lindemuthianum.

The recent cloning of plant resistance (R) genes and the sequencing of resistance gene clusters have shed light on the molecular evolution of R genes. However, up to now, no attempt has been made to correlate this molecular evolution with the host-pathogen coevolution process at the population level. Cross-inoculations were carried out between 26 strains of the fungal pathogen Colletotrichum lindemuthianum and 48 Phaseolus vulgaris plants collected in the three centers of diversity of the host species. A high level of diversity for resistance against the pathogen was revealed. Most of the resistance specificities were overcome in sympatric situations, indicating an adaptation of the pathogen to the local host. In contrast, plants were generally resistant to allopatric strains, suggesting that R genes that were efficient against exotic strains but had been overcome locally were maintained in the plant genome. These results indicated that coevolution processes between the two protagonists led to a differentiation for resistance in the three centers of diversity of the host. To improve our understanding of the molecular evolution of these different specificities, a recombinant inbred (RI) population derived from two representative genotypes of the Andean (JaloEEP558) and Mesoamerican (BAT93) gene pools was used to map anthracnose specificities. A gene cluster comprising both Andean (Co-y; Co-z) and Mesoamerican (Co-9) host resistance specificities was identified, suggesting that this locus existed prior to the separation of the two major gene pools of P. vulgaris. Molecular analysis revealed a high level of complexity at this locus. It harbors 11 restriction fragment length polymorphisms when R gene analog (RGA) clones are used. The relationship between the coevolution process and diversification of resistance specificities at resistance gene clusters is discussed.

Amino Acid Sequence↗

PubMed1992

Limited T-cell receptor beta-chain diversity of a T-helper cell type 1-like response to Mycobacterium leprae.

Delayed-type hypersensitivity (DTH) is the standard measure of T-cell responsiveness to infectious organisms. For leprosy, the Mitsuda reaction, a local immune response to cutaneous challenge with Mycobacterium leprae, is considered to represent a measure of DTH against the pathogen. We analyzed the diversity of the T-cell receptor beta-chain repertoire in Mitsuda reactions to determine the breadth of the mycobacterial antigens involved. The polymerase chain reaction was used to compare V beta usage in the Mitsuda reaction T-cell lines established and unstimulated peripheral blood. These molecular analyses revealed a skewed T-cell receptor V beta gene usage in the Mitsuda reaction and in T-cell lines from lesions. To examine the reactivity of T cells from these lesions, T-cell lines were tested against the available native and recombinant antigens of M. leprae. T-cell lines derived from Mitsuda reactions responded more strongly to the 10-kDa M. leprae antigen, a homolog of GroES in Escherichia coli, than to other M. leprae proteins. T-cell lines were also shown to proliferate strongly in response to the 17- and 3-kDa proteins. The pattern of the lymphokine mRNA of these cells was reminiscent of the pattern of murine TH1 cells, positive for interleukin-2 and gamma interferon and weakly positive for interleukin-4. These data indicate that a limited array of T cells, perhaps recognizing stress proteins, secrete a type 1 lymphokine profile in the DTH response to mycobacteria.

Antigens, Bacterial↗

PubMed2004

Identification of allelic variants of the bovine immune regulatory molecule CEACAM1 implies a pathogen-driven evolution.

Carcinoembryonic antigen-related cell adhesion molecule (CEACAM1), the primordial member of the carcinoembryonic antigen (CEA) family, functions as a MHC-independent natural killer (NK) cell inhibitory receptor, regulates T and B cell proliferation, and induces dendritic cell (DC) maturation. Despite these fundamental functions, CEACAM1 and most of the CEA family members differ significantly in primates and rodents. A number of diverse murine and human pathogens use CEACAM1 as a cellular receptor, indicating that the observed species-specific differences are the result of divergent molecular pathogen/host coevolution. To gain deeper insight into its evolution and function, we cloned CEACAM1 cDNA from cattle as a representative of a third mammalian order. Bovine CEACAM1 differs considerably from rodent and primate CEACAM1 due to deletion of the B domain exon which was most likely caused by insertion of LINE/SINE sequences and reveals alternative splicing within the transmembrane exon. However, the characteristic long and short isoforms exist which contain or lack the typical immunoreceptor tyrosine-based inhibitory motifs (ITIM) in their cytoplasmic tails, respectively. Bovine peripheral blood lymphocytes (PBL) express only ITIM-containing CEACAM1 isoforms, and upregulate their expression upon stimulation, suggesting an inhibitory function in these cells. As found in rodents, two clearly distinct CEACAM1 alleles exist in cattle. In the a allele, a unique deletion of three amino acids is found in the N domain, which is important for pathogen binding in mice and humans. This is consistent with the notion that CEACAM1 serves or has served as a pathogen receptor in cattle.

Alleles↗

PubMed2002

Mechanisms of natural soil suppressiveness to soilborne diseases.

Suppressive soils are characterized by a very low level of disease development even though a virulent pathogen and susceptible host are present. Biotic and abiotic elements of the soil environment contribute to suppressiveness, however most defined systems have identified biological elements as primary factors in disease suppression. Many soils possess similarities with regard to microorganisms involved in disease suppression, while other attributes are unique to specific pathogen-suppressive soil systems. The organisms operative in pathogen suppression do so via diverse mechanisms including competition for nutrients, antibiosis and induction of host resistance. Non-pathogenic Fusarium spp. and fluorescent Pseudomonas spp. play a critical role in naturally occurring soils that are suppressive to Fusarium wilt. Suppression of take-all of wheat, caused by Gaeumannomyces graminis var. tritici, is induced in soil after continuous wheat monoculture and is attributed, in part, to selection of fluorescent pseudomonads with capacity to produce the antibiotic 2,4-diacetylphloroglucinol. Cultivation of orchard soils with specific wheat varieties induces suppressiveness to Rhizoctonia root rot of apple caused by Rhizoctonia solani AG 5. Wheat cultivars that stimulate disease suppression enhance populations of specific fluorescent pseudomonad genotypes with antagonistic activity toward this pathogen. Methods that transform resident microbial communities in a manner which induces natural soil suppressiveness have potential as components of environmentally sustainable systems for management of soilborne plant pathogens.

Antibiosis↗

PubMed2003

Pathogen self-defense: mechanisms to counteract microbial antagonism,.

Natural and agricultural ecosystems harbor a wide variety of microorganisms that play an integral role in plant health, crop productivity, and preservation of multiple ecosystem functions. Interactions within and among microbial communities are numerous and range from synergistic and mutualistic to antagonistic and parasitic. Antagonistic and parasitic interactions have been exploited in the area of biological control of plant pathogenic microorganisms. To date, biocontrol is typically viewed from the perspective of how antagonists affect pathogens. This review examines the other face of this interaction: how plant pathogens respond to antagonists and how this can affect the efficacy of biocontrol. Just as microbial antagonists utilize a diverse arsenal of mechanisms to dominate interactions with pathogens, pathogens have surprisingly diverse responses to counteract antagonism. These responses include detoxification, repression of biosynthetic genes involved in biocontrol, active efflux of antibiotics, and antibiotic resistance. Understanding pathogen self-defense mechanisms for coping with antagonist assault provides a novel approach to improving the durability of biologically based disease control strategies and has implications for the deployment of transgenes (microorganisms or plants).

Bacteria↗

PubMed2001

ABH and Lewis histo-blood group antigens, a model for the meaning of oligosaccharide diversity in the face of a changing world.

Antigens of the ABH and Lewis histo-blood group family have been known for a long time. Yet their biological meaning is still largely obscure. Based on the available knowledge about the genes involved in their biosynthesis and about their tissue distribution in humans and other mammals, we discuss here the selective forces that may maintain or propagate these oligosaccharide antigens. The ABO, alpha 1,2fucosyltransferase and alpha 1,3fucosyltransferase enzyme families have been generated by gene duplications. Members of these families contribute to biosynthesis of the antigens through epistatic interactions. We suggest that the highly polymorphic genes of each family provide intraspecies diversity that allows coping with diverse and rapidly evolving pathogens. In contrast, the genes of low frequency polymorphism are expected to play roles at the cellular level, although they may be dispensable at the individual level. In addition, some members of these three gene families are expected to be functionally redundant and may either provide a reservoir for additional diversity in the future or become inactivated. We also discuss the role of the ABH and Lewis histo-blood group antigens in pathologies such as cancer and cardiovascular diseases, but argue that it is merely incidental and devoid of evolutionary impact.

ABO Blood-Group System↗

PubMed2002

Overexpression, purification, and site-directed spin labeling of the Nramp metal transporter from Mycobacterium leprae.

It has long been recognized that the pathogenicity of a broad range of intracellular parasites depends on the availability of transition metal ions, especially iron. Nramp1 (natural resistance-associated macrophage protein 1), a proton-coupled divalent metal ion transporter, has been identified as a controlling factor in the resistance or susceptibility to infection with a diverse range of intracellular pathogens such as Toxoplasma, Salmonella, Mycobacterium, and Leishmania. The role of divalent metal ion transport is even more compelling given the existence of Nramp homologs in several intracellular parasites, such as mycobacteria. We have confirmed the functional homology of the Nramp homologue from Mycobacterium leprae by using a yeast complementation assay for divalent cation uptake. To facilitate a concerted biochemical and structural analysis of this important class of transporters, the M. leprae Nramp was expressed in Escherichia coli. Dual affinity tags were engineered at the N and C termini to allow for isolation of full-length protein at >95% purity. Site-directed spin labeling of Cys-299 reveals a flexible hinge-like domain. A weak dipolar interaction is detected between the nitroxide and paramagnetic transition ions, indicating this position is approximately 19 A from the nearest high affinity binding site.

Base Sequence↗

PubMed1993

Variation and genetic control of surface antigen expression in mycoplasmas: the Vlp system of Mycoplasma hyorhinis.

Surface antigenic diversity in the swine pathogen Mycoplasma hyorhinis is generated by random combinatorial expression and high-frequency phase variation of multiple, size-variant membrane surface lipoproteins (Vlps) which represent the major coat proteins of this wall-less procaryote. The distinctive structural basis for Vlp variation was revealed in a family of several related but divergent vlp genes. These occur in one cluster as single chromosomal copies, each encoding a conserved domain for membrane insertion and lipoprotein processing, and a divergent external domain that changes size by deletion or insertion of repetitive intragenic coding sequences while retaining a distinctive charge motif. Lack of detectable changes in restriction fragment patterns or DNA sequence of vlp structural genes during phase transitions between ON and OFF expression states ruled out long range genomic rearrangements and frameshift mutations as a means of controlling Vlp phase variation. However, highly homologous vlp promoter regions contain a homopolymeric tract of contiguous adenine residues [poly(A)] upstream of the transcriptional start site which is subject to frequent mutations altering its length. These mutations are the only sequence changes detected during phase transitions, and are highly correlated with the expression state of each vlp gene. This suggests a mechanism of transcriptional control regulating Vlp phase variation by critical changes within the poly(A) region affecting the spacing between the -10 and -35 hexamers or a putative regulator binding site. The multiple levels of structural and antigenic diversity embodied in the vlp gene family may provide essential adaptive capabilities for this wall-less microbial pathogen.

Animals↗