Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “virulence evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources
PubMed2006

Review: molecular evolution and the feasibility of an avian influenza virus becoming a pandemic strain--a conceptual shift.

During recent years, a conceptual shift took place with respect to the genetic dynamics of influenza A viruses. In difference of the widely accepted approach that avian viral strains have the capacity to infect man only after undergoing genetic reassortment within pigs, it is now contended that direct transfection of man by intact avian-harbored viral genotypes is an actual, recurrent move, which may bring bout the generation of a new pandemic strain. This cardinal conceptual shift has been propelled by the appearance in 1997 of the zoonotic avian influenza H5N1 virus--a virulent, not yet contagious strain for humans--and ostensibly followed a genuine, unprecedented path within the evolutionary paradigm of Influenza A virus. This paper suggests that direct avian-human genetic interface is a pristine fundamental within the natural history of this protean pathogen, points at earlier as well as corroborative findings leading to such postulation, and regards the course of the H5N1 virus (and alike), as a readily detectable and traceable one, presently, rather then a novel development It further examines the general feasibility of various components of that interface at large, such that give rise--whether gradually or abruptly--to pandemic genotypes, in terms of infectivity, pathogenicity and contagiousness. Within that context, the anticipated involvement of certain human-adapted antigenic subtypes is referred to, extrapolatively. Connectedly, the significance of natural ice as plausible regenerator of influenza A viruses, and its possible contribution to the emergence and reemergence of pandemic strains are accentuated.

Animals↗
PubMed2006

Presence/absence polymorphism for alternative pathogenicity islands in Pseudomonas viridiflava, a pathogen of Arabidopsis.

The contribution of arms race dynamics to plant-pathogen coevolution has been called into question by the presence of balanced polymorphisms in resistance genes of Arabidopsis thaliana, but less is known about the pathogen side of the interaction. Here we investigate structural polymorphism in pathogenicity islands (PAIs) in Pseudomonas viridiflava, a prevalent bacterial pathogen of A. thaliana. PAIs encode the type III secretion system along with its effectors and are essential for pathogen recognition in plants. P. viridiflava harbors two structurally distinct and highly diverged PAI paralogs (T- and S-PAI) that are integrated in different chromosome locations in the P. viridiflava genome. Both PAIs are segregating as presence/absence polymorphisms such that only one PAI ([T-PAI, nablaS-PAI] and [nablaT-PAI, S-PAI]) is present in any individual cell. A worldwide population survey identified no isolate with neither or both PAI. T-PAI and S-PAI genotypes exhibit virulence differences and a host-specificity tradeoff. Orthologs of each PAI can be found in conserved syntenic locations in other Pseudomonas species, indicating vertical phylogenetic transmission in this genus. Molecular evolutionary analysis of PAI sequences also argues against "recent" horizontal transfer. Spikes in nucleotide divergence in flanking regions of PAI and nabla-PAI alleles suggest that the dual PAI polymorphism has been maintained in this species under some form of balancing selection. Virulence differences and host specificities are hypothesized to be responsible for the maintenance of the dual PAI system in this bacterial pathogen.

Arabidopsis↗
PubMed1999

Genotypic analysis of Mycobacterium tuberculosis from medieval human remains.

Three medieval bone samples with osteological evidence of tuberculosis infection were analysed for the presence of DNA sequences from Mycobacterium tuberculosis using a series of PCRs. In each case amplification of IS6110 and part of the beta-subunit of RNA polymerase identified infection with a bacterium belonging to the M. tuberculosis complex. Amplification of the mtp40 genome fragment and the presence of a guanine residue at position 285 in the oxyR pseudogene, demonstrated the infecting strain to be similar to present day M. tuberculosis isolates rather than to Mycobacterium bovis. Spoligotyping, based on amplification of the direct repeat (DR) region of the mycobacterial genome, provided further evidence of similarity to M. tuberculosis and indicated a close relationship between isolates associated with two separate medieval burials. The study demonstrates the feasibility of amplifying multiple M. tuberculosis loci in ancient human remains and suggests important applications in the study of the palaeoepidemiology and virulence of tuberculosis in past populations.

Bacterial Typing Techniques↗
PubMedDate not supplied

[A mechanism for limiting reproduction influenza A virus reassortants with incomplete functional compatibility of hemagglutinin and neuraminidase gene products].

The mechanism of decrease in the level of virus accumulation in reassortants with hemagglutinin (HA) and neuraminidase (NA) genes from different parents is studied. The reassortant viruses and their passage variants do not differ by the rate of virus protein production or their stability in infected cells. Electron microscopy and titration of infectious virus in culture fluid and cell-associated virus showed that the variants selected by serial passages accumulated mainly in the culture fluid, whereas the initial reassortant virions were predominantly cell-associated. These data suggest that incomplete removal of sialic acid residues by viral neuraminidase N1 in some reassortants results in re-attachment of virions to the infected cells and thus impairs the virus dissemination, which may be regarded as a reassortant-limiting factor probably significant for virus evolution.

Animals↗
PubMed1999

The autolysin-encoding gene (lytA) of Streptococcus pneumoniae displays restricted allelic variation despite localized recombination events with genes of pneumococcal bacteriophage encoding cell wall lytic enzymes.

The lytA-encoded autolysin (N-acetylmuramoyl-L-alanine amidase) of Streptococcus pneumoniae is believed to play an important role in the pathogenesis of pneumococcal infection and has been identified as a putative vaccine target. Allelic diversity of lytA in an extensive collection of clinical isolates was assessed by restriction fragment length polymorphism and confirmatory sequencing studies. Genetic diversity within lytA is limited, especially compared to the high levels of diversity seen in other pneumococcal virulence factor genes, although small blocks generating mosaic structure were identified. Sequence comparisons with genes encoding cell wall lytic enzymes of pneumococcal bacteriophage suggest that localized recombination events have occurred between host lytA and these bacteriophage genes. These results confirm earlier suggestions that recombination between DNA encoding bacteriophage autolytic enzymes and chromosomally encoded lytA might be important in the evolution of lytA. The implications of these findings for understanding the evolution of lytA and the potential utility of LytA as a vaccine target are discussed.

Alleles↗
PubMed2006

Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae.

Extracytoplasmic solute receptors (ESRs) are important components of solute uptake systems in bacteria, having been studied extensively as parts of ATP binding cassette transporters. Herein we report the first crystal structure of an ESR protein from a functionally characterized electrochemical ion gradient dependent secondary transporter. This protein, SiaP, forms part of a tripartite ATP-independent periplasmic transporter specific for sialic acid in Haemophilus influenzae. Surprisingly, the structure reveals an overall topology similar to ATP binding cassette ESR proteins, which is not apparent from the sequence, demonstrating that primary and secondary transporters can share a common structural component. The structure of SiaP in the presence of the sialic acid analogue 2,3-didehydro-2-deoxy-N-acetylneuraminic acid reveals the ligand bound in a deep cavity with its carboxylate group forming a salt bridge with a highly conserved Arg residue. Sialic acid binding, which obeys simple bimolecular association kinetics as determined by stopped-flow fluorescence spectroscopy, is accompanied by domain closure about a hinge region and the kinking of an alpha-helix hinge component. The structure provides insight into the evolution, mechanism, and substrate specificity of ESR-dependent secondary transporters that are widespread in prokaryotes.

ATP-Binding Cassette Transporters↗
PubMed2004

Dynamics of double-stranded RNA segments in a Helicobasidium mompa clone from a tulip tree plantation.

Eighty-three isolates of the violet root rot fungus, Helicobasidium mompa, were collected in a tulip tree plantation and analyzed for the dynamics of double-stranded (ds) RNA for five years. They were divided into eight mycelial compatibility groups (MCGs). Prevalent MCGs 60 and 68 included 61 and 11 isolates, respectively. Electrophoretic profiles of dsRNA in the first year collection of MCG 60 contained no or a single large dsRNA (more than 10 kb) with or without small dsRNAs (ca. 2.0-2.5 kb). Additional dsRNA fragments, i.e., a middle dsRNA (ca. 8.0 kb) or another type of small dsRNAs, became evident within MCG 60 isolates with time. Northern hybridization revealed the relatedness of all large and middle dsRNA fragments within MCG 60 but small fragments of dsRNA were variable. Large dsRNA fragment differed from that in other MCGs even in the same field. Correlation between specific dsRNA fragments and hypovirulence was not observed. Possible explanations for the accumulation of dsRNA fragments during the growth of disease patch by MCG 60 are discussed in terms of their internal changes such as evolution of novel dsRNA fragments from pre-existing viruses or fungal genomic DNA and horizontal transmissions.

Agriculture↗
PubMed2006

Antimicrobial drugs that target human--not microbial--genotypes or phenotypes: a paradigm change in human evolutionary response to pathogen selection pressure.

Conventional antimicrobial drugs that target microbial life processes impose a selection pressure on pathogens and attenuate pathogen imposed selection pressure on human hosts. The simultaneous increase and decrease that result in pathogen and human host evolvability/adaptability, respectively, distorts the natural Darwinian evolutionary process. Such drugs may create an aberrant Darwinian genotype in human hosts that is ill prepared to resist emerging virulent pathogenic strains in the event of a decrease in host ontogenic potential. In contrast, antimicrobial drugs that target host human genes exert a selective pressure both on the human genome (without population decimation) as well as on pathogenic microbes. Such drugs maintain the evolvability/adaptability of the host in tandem with that of the pathogens in the context of Darwinian evolution. Such drugs retain the capacity of the human host to evolve genotypes that may confer resistance to future pathogenic microbial strains, to assimilate prokaryotic endosymbionts and to increase the probability of survival in the event of a decrease in host ontogenic potential.

Anti-Infective Agents↗
PubMed2002

Compensatory adaptation to the deleterious effect of antibiotic resistance in Salmonella typhimurium.

Most chromosomal mutations that cause antibiotic resistance impose fitness costs on the bacteria. This biological cost can often be reduced by compensatory mutations. In Salmonella typhimurium, the nucleotide substitution AAA42 --> AAC in the rpsL gene confers resistance to streptomycin. The resulting amino acid substitution (K42N) in ribosomal protein S12 causes an increased rate of ribosomal proofreading and, as a result, the rate of protein synthesis, bacterial growth and virulence are decreased. Eighty-one independent lineages of the low-fitness, K42N mutant were evolved in the absence of antibiotic to ameliorate the costs. From the rate of fixation of compensated mutants and their fitness, the rate of compensatory mutations was estimated to be > or = 10-7 per cell per generation. The size of the population bottleneck during evolution affected fitness of the adapted mutants: a larger bottleneck resulted in higher average fitness. Only four of the evolved lineages contained streptomycin-sensitive revertants. The remaining 77 lineages contained mutants that were still fully streptomycin resistant, had retained the original resistance mutation and also acquired compensatory mutations. Most of the compensatory mutations, resulting in at least 35 different amino acid substitutions, were novel single-nucleotide substitutions in the rpsD, rpsE, rpsL or rplS genes encoding the ribosomal proteins S4, S5, S12 and L19 respectively. Our results show that the deleterious effects of a resistance mutation can be compensated by an unexpected variety of mutations.

Adaptation, Physiological↗
PubMed2004

Approximate solution to the speed of spreading viruses.

Recently, it has been shown that the speed of virus infections can be explained by time-delayed reaction-diffusion [J. Fort and V. Méndez, Phys. Rev. Lett. 89, 178101 (2002)], but no analytical solutions were found. Here we derive formulas for the front speed, valid in appropriate limits. We also integrate numerically the evolution equations of the system. There is good agreement with both numerical and experimental speeds.

Bacteria↗
PubMed2026

Adaptation to Plant Defence in an Agricultural Insect Pest: Integrating Genome Scans and Gene Expression in the Soybean Aphid Reveals Multi-Genic Pathways.

In agroecosystems, intense selection pressures cause species to adapt and spread, often leading to the evolution and persistence of pests. Understanding how pests rapidly adapt can help develop sustainable strategies for their management and improve agroecosystem health. Pest adaptation involves stable variations in DNA sequence, as well as dynamic shifts in gene expression, often mediated by non-coding regulatory elements. We examined adaptation to plant defences in the soybean aphid, Aphis glycines, in which virulent aphids have overcome plant defences and avirulent aphids have not. Previous data with laboratory colonies suggested that virulent aphids have higher overall gene expression, including transposable elements, some of which influence gene regulation. However, we lack information on how genetic variation in natural populations impacts adaptation and potentially gene regulation. We integrated population genome scans of field-collected, soybean aphid populations with gene expression profiles of virulent and avirulent laboratory colonies to uncover connections between genetic differentiation and gene regulation for virulence. Genome scan methods found 2144 single nucleotide polymorphisms (SNPs) with significant genetic differentiation (i.e., outliers) in field-collected populations. These SNPs were near 1004 genes, representing 5.16% of the effective number of genes. Based on previous RNA-Seq data with laboratory colonies, we found 3160 genes and 147 long non-coding RNAs (lncRNAs) with differential expression among virulent and avirulent biotypes. By integrating both data sets, we identified 16 genes and 5 long non-coding RNAs with differential expression and that were associated with an outlier SNP (within 10 kbp). We validated SNPs with additional field collected aphids and found an aphid clone with stronger virulence than our laboratory virulent colony, surviving on 2 different aphid-resistant soybean varieties. This new virulent clone had fixed allele differences at 9 SNPs compared to our avirulent and other virulent colony. Field collected soybean aphids matching the phenotype of this new virulent clone had significant genetic differentiation with 3 outlier SNPs near genes related to zinc transport and lachesin compared to field collected avirulent aphids. Our entire data reinforced the importance of a potential multi-genetic response to overcome plant defence and generates new insights into complex genetic and regulatory mechanisms involved in insect-plant interactions.

Animals↗
PubMed1996

The conjugal transfer system of Agrobacterium tumefaciens octopine-type Ti plasmids is closely related to the transfer system of an IncP plasmid and distantly related to Ti plasmid vir genes.

We have determined the DNA sequences of two unlinked regions of octopine-type Ti plasmids that contain genes required for conjugal transfer. Both regions previously were shown to contain sequences that hybridize with tra genes of the nopaline-type Ti plasmid pTiC58. One gene cluster (designated tra) contains a functional oriT site and is probably required for conjugal DNA processing, while the other gene cluster (designated trb) probably directs the synthesis of a conjugal pilus and mating pore. Most predicted Tra and Trb proteins show relatively strong sequence similarity (30 to 50% identity) to the Tra and Trb proteins of the broad-host-range IncP plasmid RP4 and show significantly weaker sequence similarity to Vir proteins found elsewhere on the Ti plasmid. An exception is found in the Ti plasmid TraA protein, which is predicted to be a bifunctional nickase-helicase that has no counterpart in IncP plasmids or among Vir proteins but has homologs in at least six other self-transmissible and mobilizable plasmids. We conclude that this Ti plasmid tra system evolved by acquiring genes from two or three different sources. A similar analysis of the Ti plasmid vir region indicates that it also evolved by appropriating genes from at least two conjugal transfer systems. The widely studied plasmid pTiA6NC previously was found to be nonconjugal and to have a 12.65-kb deletion of DNA relative to other octopine-type Ti plasmids. We show that this deletion removes the promoter-distal gene of the trb region and probably accounts for the inability of this plasmid to conjugate.

Agrobacterium tumefaciens↗
PubMed2001

Polymorphism of Bordetella pertussis isolates circulating for the last 10 years in France, where a single effective whole-cell vaccine has been used for more than 30 years.

We compared Bordetella pertussis isolates collected in France over the last 10 years, the vaccine strains used for more than 30 years, and isolates collected before the introduction of generalized vaccination. The analysis included serotyping, pulsed-field gel electrophoresis of chromosomal DNA after digestion with XbaI and SpeI, and sequencing of the pt S1 gene, encoding the S1 subunit of pertussis toxin, and the prn gene, encoding the adhesin pertactin. We found that the incidence of infection increases every 3 years. Ninety-five per cent of the isolates analyzed express type 3 fimbriae. Most of the isolates circulating since 1991, unlike the vaccinal strains, express a type A pertussis toxin and a type 2 pertactin. The isolates could be classified into five major groups by pulsed-field gel electrophoresis. Most of these groups correlated with the pertactin type expressed by the isolates. Pulsed-field gel electrophoresis is more discriminative than sequencing particular genes since it could differentiate isolates expressing type 2 pertactin into two subgroups: those circulating in 1993 to 1997 and those circulating in 1997 to 2001. This observation suggests that there has been continuous evolution of the B. pertussis population.

Bacterial Outer Membrane Proteins↗
PubMed2025

Expansion of the functional genomics GRACE library reveals genes relevant for temperature-dependent fitness in Candida albicans.

A small percentage of species in the fungal kingdom can cause devastating infections in humans, with Candida albicans reigning as a leading cause of systemic disease. One of the key virulence phenotypes for pathogenic fungi is the ability to survive at host body temperature; however, a comprehensive understanding of the mechanisms that orchestrate thermal adaptation in fungi remains incomplete. In this study, we expand the largest functional genomics resource in C. albicans, reaching 71.3% coverage of the entire genome, and perform screens under six different temperatures to identify genes important for temperature-dependent fitness. We describe the function of genes involved in translation (GAR1), splicing (C1_11680C or YSF3), and cell cycle progression (C6_00110C or RHT1) in enabling fungal survival at both low and high temperatures. Through experimental evolution, we also show that C. albicans can rapidly overcome deleterious mutations and adapt to extreme temperature environments. Overall, our study highlights the transformative potential of genome-wide functional genomics to uncover critical vulnerabilities in pathogenic fungi.

Genomics↗
PubMed2005

Spatial invasion by a mutant pathogen.

Imagine a pathogen that is spreading radially as a circular wave through a population of susceptible hosts. In the interior of this circular region, the infection dies out due to a subcritical density of susceptibles. If a mutant pathogen, having some advantage over wild-type pathogens, arises in this region it is likely to die out without leaving a noticeable trace. Mutants that arise closer to the infection wavefront have access to more susceptible hosts and thus are more likely to become established and perhaps (locally) out-compete the original pathogen. Among the factors (position, transmission rate, pathogen-induced death rate) that influence the fate of a mutant, which are most important? What does this tell us about the types of mutants that are likely to invade and become established? How do such tendencies serve to steer the evolution of pathogens in a spatial setting? Do different types of models of the same phenomena lead to similar conclusions? We address these issues from the point of view of an individual-based stochastic spatial model of host-pathogen interactions. We consider the probability of a successful invasion by a single mutant as a function of the transmissibility and virulence strengths and the mutant position in the wavefront. Next, for a version of the model in which mutations arise spontaneously, we obtain analytical and simulation results on the mean time to a successful invasion. We also use our model predictions to gain insight into experimental data on bacteriophage plaques. Finally, we compare our results to those based on ordinary and partial differential equations to better understand how different models might influence our predictions on the fate of a mutant pathogen.

Animals↗
PubMed2003

MgtC as a horizontally-acquired virulence factor of intracellular bacterial pathogens: evidence from molecular phylogeny and comparative genomics.

MgtC is a virulence factor required for intramacrophage survival and growth in low Mg2+ medium in two pathogens that are not phylogenetically related, Salmonella typhimurium and Mycobacterium tuberculosis. In S. typhimurium, mgtC is carried by the SPI-3 pathogenicity island and hybridization studies have suggested that the distribution of mgtC among enterobacteria is limited. In the present study, we searched for the presence of mgtC-like sequences in eubacterial genomes. Analyses of MgtC-like proteins phylogeny and mgtC-like chromosomal context support the hypothesis that mgtC has been acquired by horizontal gene transfer repeatedly throughout bacterial evolution. In addition, the phylogenetic analysis revealed the existence of a subgroup of proteins, that includes the S. typhimurium and M. tuberculosis MgtC proteins, as well as MgtC-related proteins from other pathogens that are able to survive in macrophages, B. melitensis and Y. pestis. We propose that MgtC has a similar function in all these distantly related pathogens, most likely providing the ability to grow in a low Mg2+ environment.

Amino Acid Sequence↗
PubMed1996

Glycoproteins E2 of the Venezuelan and eastern equine encephalomyelitis viruses contain multiple cross-reactive epitopes.

Enzyme immunoassay (EIA) with sixty types of monoclonal antibodies (MAbs) was used to study cross-reactive epitopes on the attenuated and virulent strains of the Eastern equine encephalomyelitis (EEE) and Venezuelan equine encephalomyelitis (VEE) viruses. All three structural proteins of the EEE and VEE viruses were demonstrated to have both cross-reactive and specific antigenic determinants. The glycoprotein E1 of EEE and VEE viruses possesses three cross-reactive epitopes for binding to MAbs. The glycoprotein E2 has a cluster of epitopes for 20 cross-reacting MAbs produced to EEE and VEE viruses. Cross-reactive epitopes were localised within five different sites of glycoprotein E2 of VEE virus and within four sites of that of the EEE virus. There are no cross-neutralising MAbs to the VEE and EEE viruses. Only one type of the protective Mabs was able to cross-protect mice against lethal infection by the virulent strains of the VEE and EEE viruses. Eight MAbs blocked the hemagglutination activity (HA) of both viruses. Antigenic alterations of neutralising and protective sites were revealed for all attenuated strains of the VEE and EEE viruses. Comparative studies of the E2 proteins amino acid sequences show that the antigenic modifications observed with the attenuated strains of the VEE virus may be caused by multiple amino acid changes in positions 7, 62, 120, 192 and 209-213. The escape-variants of the VEE virus obtained with cross-reactive MAbs 7D1, 2D4 and 7A6 have mutations of the E2 protein at positions 59, 212-213 and 232, respectively. Amino acid sequences in these regions of the VEE and EEE viruses are not homologous. These observations indicate that cross-reactive MAbs are capable of recognising discontinuous epitopes on the E2 glycoprotein.

Amino Acid Sequence↗
PubMed1988

The replication, partition and yop regulation of the pYV plasmids are highly conserved in Yersinia enterocolitica and Y. pseudotuberculosis.

The replication genes (rep) of the virulence plasmid pYVe439-80 of Yersinia enterocolitica were localized and characterized by restriction endonuclease analysis. Comparison with pIB1, a virulence plasmid of Y. pseudotuberculosis, indicates that while the plasmids carry homologous rep genes their location with respect to the highly conserved 'calcium region' is different. This replication function is thermosensitive. Mini-derivatives of pYVe439-80 appear to be rather unstable. The region of pYVe439-80 containing homology to the incD determinant of F was shown to contain a plasmid-stabilization system (par). The region encoding par was characterized by restriction endonuclease analysis. pIB1 contained an homologous par region but located differently. The pYV plasmids thus underwent rearrangements during their divergent evolution. While the positions of rep and par in the two plasmids are inverted with respect to the surrounding loci, our determination of the orientation of each locus rules out the hypothesis of a simple inversion of a quadrant of pYV. The gene encoding YOP5, a 26 kDa protein encoded by pIB1, was cloned on a mobilizable vector and introduced in Y. enterocolitica W22708 containing pYVe227 (indistinguishable from pYVe439-80), mutated in the homologous gene. The recombinant Y. enterocolitica secreted YOP5. Hence, the transcriptional activation and secretion systems of pYVe227 act on a yop gene from pIB1 and on its product, indicating that these systems are interchangeable.

Genes, Bacterial↗