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At least 1,369 records · Page 76Linked to original sources
PubMed2002

Large-scale structure-function analysis of the Arabidopsis RPM1 disease resistance protein.

The Arabidopsis RPM1 gene confers resistance against Pseudomonas syringae expressing either the AvrRpm1 or the AvrB type III effector protein. We present an exhaustive genetic screen for mutants that no longer recognize avrRpm1. Using an inducible avrRpm1 expression system, we identified 110 independent mutations. These mutations represent six complementation groups. None discriminates between avrRpm1 and avrB recognition. We identified 95 rpm1 alleles and present a detailed structure--function analysis of the RPM1 protein. Several rpm1 mutants retain partial function, and we deduce that their residual activity is dependent on the level of avrRpm1 signal. In these mutants, the hypersensitive response remains activated if the signal goes above a certain threshold. Missense mutations in rpm1 are highly enriched in the nucleotide binding domain, suggesting that this region plays a key role either in the hypersensitive response associated with RPM1 activation or in RPM1 stability. Cluster analysis of rpm1 alleles defines functionally important residues that are highly conserved between nucleotide binding site leucine-rich repeat R proteins and those that are unique to RPM1. Regions of RPM1 to which no loss-of-function alleles map may represent domains in which variation is tolerated and may contribute to the evolution of new R gene specificities.

Alleles↗
PubMedDate not supplied

Characterization of trichomonad species and strains by PCR fingerprinting.

The random amplified polymorphic DNA (RAPD) technique was used for phylogenetic analysis of trichomonads, for intraspecies genealogical study of Trichomonas vaginalis strains, and for assessment of intrastrain polymorphism in Trichomonas vaginalis. The phylogenetic tree for 12 trichomonad species showed certain discrepancies with current models of trichomonad evolution. However, it shows that RAPD traits retain phylogenetically relevant information. The results of intraspecies analyses of 18 Trichomonas vaginalis strains suggested some concordance between the genetic relationship of strains and their geographic origin. They also suggested a concordance between the strain genetic relationships and the resistance to metronidazole. A concordance was also found with respect to the severity of disease observed in donor patients but not with the results of laboratory virulence assays. No concordance was found between genetic relationship of strains and strain infection with a dsRNA Trichomonas vaginalis virus (TVV). The latter suggests that TVV might be transmitted horizontally among Trichomonas vaginalis populations. The identity of RAPD patterns of clones isolated from in vitro cultures and those of the cultures reisolated independently from the same patient within a period of six weeks suggests that individual Trichomonas vaginalis strains are not polymorphic and that the RAPD patterns are stable. Therefore, the RAPD technique seems useful for addressing various clinically relevant issues.

Animals↗
PubMed1996

Adaptive evolution of human immunodeficiency virus-type 1 during the natural course of infection.

The rate of progression to disease varies considerably among individuals infected with human immunodeficiency virus-type 1 (HIV-1). Analyses of semiannual blood samples obtained from six infected men showed that a rapid rate of CD4 T cell loss was associated with relative evolutionary stasis of the HIV-1 quasispecies virus population. More moderate rates of CD4 T cell loss correlated with genetic evolution within three of four subjects. Consistent with selection by the immune constraints of these subjects, amino acid changes were apparent within the appropriate epitopes of human leukocyte antigen class I-restricted cytotoxic T lymphocytes. Thus, the evolutionary dynamics exhibited by the HIV-1 quasispecies virus populations under natural selection are compatible with adaptive evolution.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Recombination hotspots and population structure in Plasmodium falciparum.

Understanding the influences of population structure, selection, and recombination on polymorphism and linkage disequilibrium (LD) is integral to mapping genes contributing to drug resistance or virulence in Plasmodium falciparum. The parasite's short generation time, coupled with a high cross-over rate, can cause rapid LD break-down. However, observations of low genetic variation have led to suggestions of effective clonality: selfing, population admixture, and selection may preserve LD in populations. Indeed, extensive LD surrounding drug-resistant genes has been observed, indicating that recombination and selection play important roles in shaping recent parasite genome evolution. These studies, however, provide only limited information about haplotype variation at local scales. Here we describe the first (to our knowledge) chromosome-wide SNP haplotype and population recombination maps for a global collection of malaria parasites, including the 3D7 isolate, whose genome has been sequenced previously. The parasites are clustered according to continental origin, but alternative groupings were obtained using SNPs at 37 putative transporter genes that are potentially under selection. Geographic isolation and highly variable multiple infection rates are the major factors affecting haplotype structure. Variation in effective recombination rates is high, both among populations and along the chromosome, with recombination hotspots conserved among populations at chromosome ends. This study supports the feasibility of genome-wide association studies in some parasite populations.

Africa↗
PubMed2002

Horizontal transfer of the plant virulence gene, nec1, and flanking sequences among genetically distinct Streptomyces strains in the Diastatochromogenes cluster.

Evidence for the horizontal transfer of a pathogenicity island (PAI) carrying the virulence gene nec1 and flanking sequences among Streptomyces strains in the Diastatochromogenes cluster is presented. Plant-pathogenic, thaxtomin-producing Streptomyces strains, previously classified as S. scabiei based on the conventionally used phenotypic characteristics, were found to be genetically distinct from the type strain of S. scabiei based on DNA relatedness and 16S rDNA sequence analysis. Pairwise DNA-DNA hybridizations between some of these strains and the S. scabiei type strain were as low as 36%, a value much below what is conventionally accepted for species identity (70%). The sequence of the nec1 gene, however, was identical in all the S. scabiei and S. scabiei-like strains tested, irrespective of their DNA relatedness to the type strain of S. scabiei, their geographic origin, or the isolation host. Furthermore, a 26-kb DNA fragment including and flanking nec1 was also conserved among these strains based on restriction and Southern analyses. These data indicate that the etiology of potato scab is more complex than previously recognized; this result has important implications for potato scab management strategies. Previous research has suggested that horizontal transfer of a PAI was the mechanism for evolution of pathogenicity in S. acidiscabies and S. turgidiscabies, species that lie outside of the Diastatochromogenes cluster. Data presented here support this model and indicate that PAI transfer also has occurred frequently in species closely related to S. scabiei.

Arachis↗
PubMed2005

Mutations in Turnip mosaic virus genomes that have adapted to Raphanus sativus.

The genetic basis for virulence in potyviruses is largely unknown. Earlier studies showed that there are two host types of Turnip mosaic virus (TuMV); the Brassica/Raphanus (BR)-host type infects both Brassica and Raphanus systemically, whereas the Brassica (B)-host type infects Brassica fully and systemically, but not Raphanus. The genetic basis of this difference has been explored by using the progeny of an infectious clone, p35Tunos; this clone is derived from the UK1 isolate, which is of the B-host type, but rarely infects Raphanus systemically and then only asymptomatically. Two inocula from one such infection were adapted to Raphanus by passaging, during which the infectivity and concentration of the virions of successive infections increased. The variant genomes in the samples, 16 in total, were sequenced fully. Four of the 39 nucleotide substitutions that were detected among the Raphanus sativus-adapted variant genomes were probably crucial for adaptation, as they were found in several variants with independent passage histories. These four were found in the protein 1 (P1), protein 3 (P3), cylindrical inclusion protein (CI) and genome-liked viral protein (VPg) genes. One of four 'parallel evolution' substitutions, 3430G-->A, resulted in a 1100Met-->Ile amino acid change in the C terminus of P3. It seems likely that this site is important in the initial stages of adaptation to R. sativus. Other independent substitutions were mostly found in the P3, CI and VPg genes.

Adaptation, Physiological↗
PubMed2003

Secretins of Pseudomonas aeruginosa: large holes in the outer membrane.

Pseudomonas aeruginosa produces a large number of exoproteins, ranging from the ADP-ribosyltransferases exotoxin A and ExoS to degradative enzymes, such as elastase and chitinase. As it is a gram-negative bacterium, P. aeruginosa must be able to transport these exoproteins across both membranes of the cell envelope. In addition, also proteins that are part of cellular appendages, such as type IV pili and flagella, have to cross the cell envelope. Whereas the majority of the proteins transported across the inner membrane are dependent on the Sec channel, the systems for translocation across the outer membrane seem to be more diverse. Gram-negative bacteria have invented a number of different strategies during the course of evolution to achieve this goal. Although these transport machineries seem to be radically different, many of them actually depend on a member of the secretin protein family for their function. Recent results show that secretins form a large complex in the outer membrane, which constitutes the actual translocation channel. Understanding the working mechanism of this protein translocation channel could open up new strategies to target molecular machineries at the heart of many important virulence factors.

Bacterial Outer Membrane Proteins↗
PubMedDate not supplied

A molecular strategy for the study of bacterial invasion.

Bacterial populations are often clonal, and even within a bacterial species, the frequency of gene exchange and recombination is quite low. Consequently, mobile genetic elements--plasmids, bacteriophages, and transposons--have been the central factors in the evolution of pathogenic traits. One central feature of pathogenicity, the capacity to enter epithelial cells, is encoded by the bacterial chromosome of Yersinia pseudotuberculosis but by plasmid genes in enteroinvasive Escherichia coli. A single Yersinia gene, inv, which encodes a single 107,000-dalton protein, can be cloned in E. coli K12, and its presence is sufficient to permit the bacteria to enter cultured human cells. In contrast, fully 70 kilobases of a virulence plasmid from enteroinvasive E. coli must be transferred to E. coli K12 to achieve the same result. While researchers are at the early stages of understanding microbial entry into host cells, they can now investigate the molecular basis of this event in greater detail than has previously been possible.

Animals↗
PubMed2006

Dengue and dengue haemorrhagic fever: implications of host genetics.

Little is known of the role of human leucocyte antigen (HLA) alleles or non-HLA alleles in determining resistance, susceptibility or the severity of acute viral infections. Dengue fever (DF) and dengue haemorrhagic fever (DHF) are suitable models for immunogenetic studies, yet only superficial efforts have been made to study dengue disease to date. DF and DHF can be caused by both primary and secondary infection by any of the four serotypes of the dengue virus. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virus virulence. Variations in immune response, often associated with polymorphism in the human genome, can now be detected. Data on the influence of human genes in DF and DHF are discussed here in relation to (1) associations between HLA polymorphism and dengue disease susceptibility or resistance, (2) protective alleles influencing progression to severe disease, (3) alleles restricting CD4(+) and CD8(+) T lymphocytes, and (4) non-HLA genetic factors that may contribute to DHF evolution. Recent discoveries regarding genetic associations in other viral infections may provide clues to understanding the development of end-stage complications in dengue disease. The scanty positive data presented here indicate a need for detailed genetic studies in different ethnic groups in different countries during the acute phase of DF and DHF on a larger number of patients.

Alleles↗
PubMed2006

Whole-genome expression profiling defines the HrpL regulon of Pseudomonas syringae pv. tomato DC3000, allows de novo reconstruction of the Hrp cis clement, and identifies novel coregulated genes.

Pseudomonas syringae pv. tomato DC3000 is a model pathogen of tomato and Arabidopsis that uses a hypersensitive response and pathogenicity (Hrp) type III secretion system (T3SS) to deliver virulence effector proteins into host cells. Expression of the Hrp system and many effector genes is activated by the HrpL alternative sigma factor. Here, an open reading frame-specific whole-genome microarray was constructed for DC3000 and used to comprehensively identify genes that are differentially expressed in wild-type and deltahrpL strains. Among the genes whose differential regulation was statistically significant, 119 were upregulated and 76 were downregulated in the wild-type compared with the deltahrpL strain. Hierarchical clustering revealed a subset of eight genes that were upregulated particularly rapidly. Gibbs sampling of regions upstream of HrpL-activated operons revealed the Hrp promoter as the only identifiable regulatory motif and supported an iterative refinement involving real-time polymerase chain reaction testing of additional HrpL-activated genes and refinements in a hidden Markov model that can be used to predict Hrp promoters in P. syringae strains. This iterative bioinformatic-experimental approach to a comprehensive analysis of the HrpL regulon revealed a mix of genes controlled by HrpL, including those encoding most type III effectors, twin-arginine transport (TAT) substrates, other regulatory proteins, and proteins involved in the synthesis or metabolism of phytohormones, phytotoxins, and myo-inositol. This analysis provides an extensively verified, robust method for predicting Hrp promoters in P. syringae genomes, and it supports subsequent identification of effectors and other factors that likely are important to the host-specific virulence of P. syringae.

Bacterial Proteins↗
PubMed2002

Expression and characterization of flagella in nonmotile enteroinvasive Escherichia coli isolated from diarrhea cases.

We report that enteroinvasive Escherichia coli (EIEC) serotypes considered to be nonmotile produce an unusually large (77 kDa) flagellin that is assembled into functional flagellum filaments that allow the bacteria to swim in modified motility agar. The EIEC flagellin showed N-terminal identity to most common enterobacterial flagellins, especially those of the E. coli H7 serotype. These data are important in terms of the epidemiology, evolution, and biology of EIEC.

Amino Acid Sequence↗
PubMed1993

Identification of a G protein alpha subunit from Neurospora crassa that is a member of the Gi family.

Heterotrimeric G proteins, consisting of alpha, beta, and gamma subunits, are implicated in major signal transduction pathways controlling a diversity of functions in eukaryotic organisms. In the filamentous fungus Neurospora crassa, G proteins are implicated in the regulation of several environmental responses. As a first step in studying the role of G proteins in these processes, we have cloned the genes for two alpha subunits, gna-1 and gna-2, from Neurospora. The genes are located on different chromosomes and are differentially regulated during asexual development. The encoded proteins (Gna-1 and Gna-2) are the same size as members of the Gi-alpha family (approximately 40 kDa). The Gna-1 protein sequence is 55% identical overall to members of the Gi family and contains the consensus sequences for ADP-ribosylation by pertussis toxin and incorporation of myristic acid, which are found in this group. These properties make Gna-1 the first identified microbial alpha subunit to be a member of any class. Furthermore, incubation of a N. crassa plasma membrane fraction with pertussis toxin results in ADP-ribosylation of a protein substrate which is the approximate size of Gna-1. The predicted Gna-2 protein sequence does not share a high degree of sequence identity with the Gi class. However, the coding region contains at least one intron in a position conserved in the Gi family. We propose that the Gi family of alpha subunits is ancient and during evolution may have first appeared in filamentous fungi.

Adenosine Diphosphate Ribose↗
PubMed2005

Whole-genome sequencing of staphylococcus haemolyticus uncovers the extreme plasticity of its genome and the evolution of human-colonizing staphylococcal species.

Staphylococcus haemolyticus is an opportunistic bacterial pathogen that colonizes human skin and is remarkable for its highly antibiotic-resistant phenotype. We determined the complete genome sequence of S.haemolyticus to better understand its pathogenicity and evolutionary relatedness to the other staphylococcal species. A large proportion of the open reading frames in the genomes of S.haemolyticus, Staphylococcus aureus, and Staphylococcus epidermidis were conserved in their sequence and order on the chromosome. We identified a region of the bacterial chromosome just downstream of the origin of replication that showed little homology among the species but was conserved among strains within a species. This novel region, designated the "oriC environ," likely contributes to the evolution and differentiation of the staphylococcal species, since it was enriched for species-specific nonessential genes that contribute to the biological features of each staphylococcal species. A comparative analysis of the genomes of S.haemolyticus, S.aureus, and S.epidermidis elucidated differences in their biological and genetic characteristics and pathogenic potentials. We identified as many as 82 insertion sequences in the S.haemolyticus chromosome that probably mediated frequent genomic rearrangements, resulting in phenotypic diversification of the strain. Such rearrangements could have brought genomic plasticity to this species and contributed to its acquisition of antibiotic resistance.

Biological Evolution↗
PubMed1992

Replication cycle of Bacillus subtilis hydroxymethyluracil-containing phages.

The present review focuses on phage 2C, a member of a family of virulent phages that multiply in Bacillus subtilis. The best known members of this group are SPO1, phi e, H1, 2C, SP8, and SP82, the genomes of which are made of double-stranded DNA of about 150 kilobase pairs (kbp). The two DNA strands have different buoyant densities. Moreover, thymine (T) is completely replaced by hydroxymethyluracil (hmUra). Comparison of the phage DNAs has shown that both base substitutions and deletions have contributed to the evolution of their genomes. In addition, all of the hmUra-phage genomes contain colinear redundant ends, amounting to 10% of total bases. Two lines of evidence suggest that the redundant ends of 2C DNA, in spite of extensive homology, contain unique sequences. Further studies focused on DNA replication during the lytic cycle. The semiconservative replication of the infecting viral genome is followed by extensive recombination. At the level of replication forks, viral DNA synthesis is discontinuous on both strands during the whole cycle. Deoxythymidinetriphosphate, required for viral DNA synthesis in permeabilized infected bacteria, was incorporated in small amounts into phage DNA. The putative primary origin of replication has been cloned and localized on the viral genome. Some viral promoters have been successfully cloned in Escherichia coli. These sequences, however, did not promote transcription in B. subtilis. The abnormal base might be required for promoter activity in the natural host.

Bacillus Phages↗
PubMed1998

Prevention of infection in immunocompromised hosts.

The prevention of infection in patients with cancer has changed tremendously over the last decade, but remains in evolution. Despite many clinical trials examining the role of antibacterial, antifungal, and antiviral prophylaxis, there is still discussion among physicians about not only which patients require prophylaxis, but also the optimal regimen. Nevertheless, many of these regimens offer the hope to prevent infection in patients with underlying neoplastic diseases. There is no therapy that is uniformly effective in all settings. This is generally due to the severity of the defects in host defenses and the virulence of the microorganism. Hopefully, the future will hold many new therapeutic options to help prevent infection in patients with cancer.

Bacterial Infections↗
PubMed1991

Ecological and genetic models of host-pathogen coevolution.

A model is presented to analyse the forces that maintain genetic polymorphism in interactions between host plants and their pathogens. Genetic variability in hosts occurs for specific resistance to different pathogen races and variability in pathogens occurs for specific virulence to different host races. The model tracks both fluctuating population sizes and changing gene frequencies. Analyses over a range of parameters show that ecological and demographic factors, such as birth and death rates, often have a more profound effect on the amount of polymorphism than genetic parameters, such as the pleiotropic costs of resistance and virulence associated with different alleles. A series of simple measures are proposed to predict the amount of genetic polymorphism expected in particular host-pathogen interactions. These measures can be used to develop and test a comparative theory of genetic polymorphism in host-pathogen coevolution.

Biological Evolution↗
PubMed2006

Cardiovirus leader proteins are functionally interchangeable and have evolved to adapt to virus replication fitness.

The leader (L) proteins encoded by picornaviruses of the genus Cardiovirus [Theiler's murine encephalomyelitis virus (TMEV) and Encephalomyocarditis virus (EMCV)] are small proteins thought to exert important functions in virus-host interactions. The L protein of persistent TMEV strains was shown to be dispensable for virus replication in vitro, but crucial for long-term persistence of the virus in the central nervous system of the mouse. The phenotype of chimeric viruses generated by exchanging the L-coding regions was analysed and it was shown that the L proteins of neurovirulent and persistent TMEV strains are functionally interchangeable in vitro and in vivo, despite the fact that L is the second most divergent protein encoded by these viruses after the L* protein. The L protein encoded by EMCV and Mengo virus (an EMCV strain) shares about 35 % amino acid identity with that of TMEV. It differs from the latter by lacking a serine/threonine-rich C-terminal domain and by carrying phosphorylated residues not conserved in the TMEV L protein. Our data show that, in spite of these differences, the L protein of Mengo virus shares, with that of TMEV, the ability to inhibit the transcription of type I interferon, cytokine and chemokine genes and to interfere with nucleocytoplasmic trafficking of host-cell proteins. Interestingly, analysis of viral RNA replication of the recombinant viruses raised the hypothesis that L proteins of TMEV and EMCV diverged during evolution to adapt to the different replication fitness of these viruses.

Adaptation, Physiological↗
PubMed2004

Intraocular lenses, bacterial adhesion and endophthalmitis prevention: a review.

Postoperative endophthalmitis following intraocular lens (IOL) implantation is still one of the most feared complications of cataract surgery. Bacterial adhesion to IOLs during their insertion is a prominent etiological factor. Polypropylene was the first biomaterial that allowed this relation of cause and effect to be proven. Following adhesion, bacteria replicate, congregate and form multiple layers of microcolonies which actually represent the basic structural unit of the biofilm. The bacteria are embedded in a slime layer. Personal photographs illustrate the different steps of biofilm formation. This slime matrix is not only an adhesive medium; it also affects virulence. Adhesion to IOLs has been studied by several in vitro studies and discrepancies can be found between them which are due to variations of experimental conditions. The strains, the incubation times and the methods all varied. Adhesion is affected by the nature of the IOLs, the isolates and the surrounding medium. Since this medium is very difficult to model because of its complexity, in vivo studies seemed essential. We have recently determined in vivo evolution of the amount of attached bacteria to five types of IOLs. Crystalline lenses from 90 domestic pigs were removed aseptically and replaced with previously infected IOLs. There have been few epidemiological studies published to determine the relationship between endophthalmitis and the IOL type. However, the perfect biomaterial that could prevent postoperative endophthalmitis does not yet exist. Globally, hydrophilic materials and hydrophobic acrylic seem to be less sticky than silicone or PMMA, but this remains to be proven clinically.

Animals↗