PubMed Health⌕ Search

Biomedical subjects

E J Feil

Publications and source records attributed to E J Feil.

12 recordsLinked to original sources
PubMed2001

A link between virulence and ecological abundance in natural populations of Staphylococcus aureus.

Staphylococcus aureus is a major cause of severe infection in humans and yet is carried without symptoms by a large proportion of the population. We used multilocus sequence typing to characterize isolates of S. aureus recovered from asymptomatic nasal carriage and from episodes of severe disease within a defined population. We identified a number of frequently carried genotypes that were disproportionately common as causes of disease, even taking into account their relative abundance among carriage isolates. The existence of these ecologically abundant hypervirulent clones suggests that factors promoting the ecological fitness of this important pathogen also increase its virulence.

Carrier State↗
PubMed2001

Recombination within natural populations of pathogenic bacteria: short-term empirical estimates and long-term phylogenetic consequences.

The identification of clones within bacterial populations is often taken as evidence for a low rate of recombination, but the validity of this inference is rarely examined. We have used statistical tests of congruence between gene trees to examine the extent and significance of recombination in six bacterial pathogens. For Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus, the congruence between the maximum likelihood trees reconstructed using seven house-keeping genes was in most cases no better than that between each tree and trees of random topology. The lack of congruence between gene trees in these four species, which include both naturally transformable and nontransformable species, is in three cases supported by high ratios of recombination to point mutation during clonal diversification (estimates of this parameter were not possible for Strep. pyogenes). In contrast, gene trees constructed for Hemophilus influenzae and pathogenic isolates of Escherichia coli showed a higher degree of congruence, suggesting lower rates of recombination. The impact of recombination therefore varies between bacterial species but in many species is sufficient to obliterate the phylogenetic signal in gene trees.

Alleles↗
PubMed2001

The relative contributions of recombination and point mutation to the diversification of bacterial clones.

Low levels of recombination in bacterial species have often been inferred from the presence of linkage disequilibrium between the alleles at different loci in the population. However, significant linkage disequilibrium is inevitable in organisms that divide by binary fission, and recombinational replacements must be very frequent, compared to point mutation, to dissipate disequilibrium. Recent studies using data from multilocus sequence typing indicate that, in many species, recombinational replacements contribute more greatly to clonal diversification than do point mutations and, in some species, recombination has been sufficient to eliminate any phylogenetic signal from gene trees. Recent efforts to improve understanding of the extent and impact of homologous recombination in the diversification of bacterial clones are discussed.

Bacteria↗
PubMed2001

Sequence type analysis and recombinational tests (START).

UNLABELLED: The 32-bit Windows application START is implemented using Visual Basic and C(++) and performs analyses to aid in the investigation of bacterial population structure using multilocus sequence data. These analyses include data summary, lineage assignment, and tests for recombination and selection. AVAILABILITY: START is available at http://outbreak.ceid.ox.ac.uk/software.htm. CONTACT: keith.jolley@ceid.ox.ac.uk

Databases, Nucleic Acid↗
PubMed2001

Recombination and the population structures of bacterial pathogens.

The population structures of bacterial species are complex and often controversial. To a large extent, this is due to uncertainty about the frequency and impact of recombination in bacteria. The existence of clones within bacterial populations, and of linkage disequilibrium between alleles at different loci, is often cited as evidence for low rates of recombination. However, clones and linkage disequilibrium are almost inevitable in species that divide by binary fission and can be present in populations where recombination is frequent. In recent years, it has become possible to directly compare rates of recombination in different species. These studies indicate that in many bacterial species, including Neisseria meningitidis, Streptococcus pneumoniae, and Staphylococcus aureus, evolutionary change at neutral (housekeeping) loci is more likely to occur by recombination than mutation and can result in the elimination of any deep-rooted phylogenetic signal. In such species, the long-term evolution of the population is dominated by recombination, but this does not occur at a sufficiently high frequency to prevent the emergence of adaptive clones, although these are relatively short-lived and rapidly diversify.

Bacterial Physiological Phenomena↗
PubMed2000

Population structure and evolutionary dynamics of pathogenic bacteria.

Evidence concerning the significance of recombination within natural bacterial populations has historically come from two main sources: multilocus enzyme electrophoresis (MLEE) and nucleotide sequence data. Here we discuss evidence from a third method, multilocus sequence typing (MLST), which is a development of MLEE based on nucleotide sequencing that combines the advantages of both approaches. MLST has confirmed both the existence of clones and the high rates of recombination for several bacterial pathogens. The data are consistent with "epidemic" population structures, where clones are superimposed upon a backdrop of frequent recombination, thus, in the short term, resisting the homogenising effect of recombination. The nature of the selective advantage of clones, however, and how this advantage relates to virulence are unclear. The current evidence also has broader implications concerning bacterial species definition, the management of antibiotic-resistant bacteria and the assessment of the dangers of releasing genetically modified organisms into the environment.

Bacteria↗
PubMed2000

Estimating recombinational parameters in Streptococcus pneumoniae from multilocus sequence typing data.

Multilocus sequence typing (MLST) is a highly discriminatory molecular typing method that defines isolates of bacterial pathogens using the sequences of approximately 450-bp internal fragments of seven housekeeping genes. This technique has been applied to 575 isolates of Streptococcus pneumoniae and identifies a number of discrete clonal complexes. These clonal complexes are typically represented by a single group of isolates sharing identical alleles at all seven loci, plus single-locus variants that differ from this group at only one out of the seven loci. As MLST is highly discriminatory, the members of each clonal complex can be assumed to have a recent common ancestor, and the molecular events that give rise to the single-locus variants can be used to estimate the relative contributions of recombination and mutation to clonal divergence. By comparing the sequences of the variant alleles within each clonal complex with the allele typically found within that clonal complex, we estimate that recombination has generated new alleles at a frequency approximately 10-fold higher than mutation, and that a single nucleotide site is approximately 50 times more likely to change through recombination than mutation. We also demonstrate how to estimate the average length of recombinational replacements from MLST data.

Alleles↗
PubMed2000

Carried meningococci in the Czech Republic: a diverse recombining population.

Population and evolutionary analyses of pathogenic bacteria are frequently hindered by sampling strategies that concentrate on isolates from patients with invasive disease. This is especially so for the gram-negative diplococcus Neisseria meningitidis, a cause of septicemia and meningitis worldwide. Meningococcal isolate collections almost exclusively comprise organisms originating from patients with invasive meningococcal disease, although this bacterium is a commensal inhabitant of the human nasopharynx and very rarely causes pathological effects. In the present study, molecular biology-based techniques were used to establish the genetic relationships of 156 meningococci isolated from healthy young adults in the Czech Republic during 1993. None of the individuals sampled had known links to patients with invasive disease. Multilocus sequence typing (MLST) showed that the bacterial population was highly diverse, comprising 71 different sequence types (STs) which were assigned to 34 distinct complexes or lineages. Three previously identified hyperinvasive lineages were present: 26 isolates (17%) belonged to the ST-41 complex (lineage 3); 4 (2.6%) belonged to the ST-11 (electrophoretic type [ET-37]) complex, and 1 (0.6%) belonged to the ST-32 (ET-5) complex. The data were consistent with the view that most nucleotide sequence diversity resulted from the reassortment of alleles by horizontal genetic exchange.

Adolescent↗
PubMed1999

The relative contributions of recombination and mutation to the divergence of clones of Neisseria meningitidis.

Multilocus sequence typing (MLST) is a recently developed nucleotide sequence-based method for the definitive assignment of isolates within bacterial populations to specific clones. MLST uses the same principles as multilocus enzyme electrophoresis and provides data that can be used to investigate aspects of the population genetics and evolution of bacterial species. We used an MLST data set consisting of the sequences of approximately 450-bp fragments from seven housekeeping loci from a large strain collection of Neisseria meningitidis to estimate the relative impact of recombination compared with point mutation in the diversification of N. meningitidis clonal complexes. 126 meningococcal isolates were assigned to 10 clonal complexes, 9 of which contained minor clonal variants. The allelic variation within each complex was classified as a recombinational exchange or a putative point mutation through a comparison of the sequences of each variant allele with that of the allele typically found in the clonal complex. The nine clonal complexes contained a total of 23 allelic variants, and analysis of the sequences of these variant alleles revealed that a single nucleotide site in a meningococcal housekeeping gene is at least 80-fold more likely to change as a result of recombination than as a result of mutation. This value is estimated to be 10-50-fold for Escherichia coli and approximately 50-fold for Streptococcus pneumoniae.

Alleles↗
PubMed1977

A comparative study of dextran-70, warfarin and low-dose heparin for the prophylaxis of thrombo-embolism following total hip replacement.

In a randomized, controlled clinical study, dextran-70, warfarin, or low-dose heparin were administered to patients undergoing total hip replacement on one surgical unit in an attempt to prevent deep venous thrombosis and pulmonary embolism. Calf vein thrombosis was detected by the 125I-fibrinogen uptake test. None of the methods prevented calf vein thrombosis (dextran-70, 51%; warfarin, 58-6%; heparin, 52-6%). Pulmonary embolism was completely prevented in patients treated with warfarin but occurred in 4% of patients treated with dextran-70 and 15-5% of those treated with low-dose heparin. The incidence of complications of therapy was small and comparable in each group. It is suggested that calf vein thrombosis is a frequent and in itself a non-serious complication of total hip replacement surgery and that emphasis might be placed more usefully on prevention of pulmonary embolism.

Aged↗
PubMedDate not supplied

Estimating the relative contributions of mutation and recombination to clonal diversification: a comparison between Neisseria meningitidis and Streptococcus pneumoniae.

Both Neisseria meningitidis and Streptococcus pneumoniae are naturally transformable species and are known to be freely recombining in the wild. Large multilocus sequence typing (MLST) datasets have been generated for these species. Here we outline an approach which exploits these data sets in order to quantify the extent of recombination, thus enabling meaningful comparisons between the two species. Two parameters are estimated; the rate at which recombination changes alleles, compared to point mutation, and the rate at which recombination changes individual nucleotide sites, compared to point mutation. Estimates for the former parameter are 4:1 in the meningococcus (i.e. alleles are changed four-fold more frequently by recombination than by mutation), and 10:1 in the pneumococcus. However, estimates for the latter parameter are at least 80:1 in the meningococcus (i.e. an individual nucleotide site is at least 80-fold more likely to change by recombination than by mutation) and 50:1 in the pneumococcus. These data imply that recombination events, compared to mutational events, may be more common in the pneumococcus than in the meningococcus. However, because it is a more diverse species, each recombinational exchange in the meningococcus results in more nucleotide changes on average.

Genetic Variation↗