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T S Whittam

Publications and source records attributed to T S Whittam.

At least 19 recordsLinked to original sources
PubMed1992

Sequencing errors and molecular evolutionary analysis.

Heuristic approaches were used to quantify the influence that sequencing errors have on estimates of nucleotide diversity, substitution rate, and the construction of genealogies. Error rates of less than 1 nucleotide/kb probably have little affect on conclusions about the evolutionary history of highly polymorphic organisms such as Drosophila and Escherichia coli, but organisms with very low nucleotide diversity, such as humans, require greater sequencing accuracy. A scan of GenBank for corrections of previous errors reveals that sequencing errors are highly nonrandom.

Animals↗
PubMed1992

Outer membrane protein patterns mark clones of Escherichia coli O2 and O78 strains that cause avian septicemia.

Major outer membrane proteins were isolated from 36 Escherichia coli strains representing six common clones of the O2 and O78 serogroups implicated in avian colisepticemia. Clonal relationships among isolates were inferred from an analysis of polymorphism at 20 enzyme-encoding loci detected by multilocus enzyme electrophoresis. For isolates of these clones, there was a high concordance (greater than 90%) between identity in multilocus genotype and major outer membrane protein patterns. The results indicate that major outer membrane protein patterns discriminate among the genetically different clonal groups that constitute the heterogeneous O2 and O78 serogroups associated with avian disease.

Alleles↗
PubMed1991

Nucleotide polymorphism and evolution in the glyceraldehyde-3-phosphate dehydrogenase gene (gapA) in natural populations of Salmonella and Escherichia coli.

Nucleotide sequences of the gapA gene, encoding the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, were determined for 16 strains of Salmonella and 13 strains of Escherichia coli recovered from natural populations. Pairs of sequences from strains representing the eight serovar groups of Salmonella differed, on average, at 3.8% of nucleotide sites and 1.1% of inferred amino acids, and comparable values for E. coli were an order of magnitude smaller (0.2% and 0.1%, respectively). The rate of substitution at synonymous sites was significantly higher for codons specifying the catalytic domain of the enzyme than for those encoding the NAD(+)-binding domain, but the nonsynonymous substitution rate showed the opposite relationship. For Salmonella, statistical tests for nonrandom clustering of polymorphic sites failed to provide evidence that intragenic recombination or gene conversion has contributed to the generation of allelic diversity. The topology of a tree constructed from the gapA sequences was generally similar to that of phylogenetic trees of the strains based on multilocus enzyme electrophoresis, but the level of divergence of gapA in Salmonella group V from other Salmonella and E. coli strains is much greater than that indicated by DNA hybridization for the genome as a whole.

Amino Acid Sequence↗
PubMed1991

Heterozygosity at individual amino acid sites: extremely high levels for HLA-A and -B genes.

The amino acid heterozygosities per site for HLA-A and -B loci are determined to be extremely high by combining population serotypic frequencies with amino acid sequences. For the 54 amino acid sites thought to have functional importance, the average heterozygosity per site is 0.301. Sixteen positions have heterozygosities greater than 0.5 at one or both loci and the frequencies of amino acids at a given position are very even, resulting in nearly the maximum heterozygosity possible. Furthermore, the high heterozygosity is concentrated in the peptide-interacting sites, whereas the sites that interact with the T-cell receptor have lower heterozygosity. Overall, these results indicate the importance of some form of balancing selection operating at HLA loci, maybe even at the individual amino acid level.

Alleles↗
PubMed1991

Reference collection of strains of the Salmonella typhimurium complex from natural populations.

A collection of 72 reference strains of the Salmonella typhimurium complex of clones recovered from a variety of hosts and environmental sources in diverse geographic locations has been established for use in studies of variation in natural populations. Included are strains of the serovars S. typhimurium, S. saintpaul, S. heidelberg, S. paratyphi B (including variety java) and S. muenchen. The strains, which have been characterized by enzyme electrophoresis for allelic variation in 24 chromosomal structural genes and represent 48 distinctive multilocus genotypes (electrophoretic types or ETs), exemplify the full range of genotypic variation in the S. typhimurium complex. Evolutionary genetic relationships among the ETs are indicated in a phylogenetic tree generated by the neighbour-joining method from a matrix of Nei's standard genetic distance.

Alleles↗
PubMed1990

Clonal relationships among classic enteropathogenic Escherichia coli (EPEC) belong to different O groups.

Fifty Escherichia coli strains belonging to nine classic EPEC (enteropathogenic E. coli) O:H serotypes from infantile diarrhea were examined for enzyme polymorphism and typed according to their multilocus genotypes. They were further examined for lipopolysaccharide (LPS) patterns by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining, for localized adhesion to HEp2 cells, and for their outer membrane protein (OMP) pattern. A very close relationship was detected among electrophoretic type, O:H serotype, biotype, LPS type, and OMP pattern. Most likely these characteristic EPEC groups (all type I) each represented bacterial clones, and furthermore they could be grouped into two genetically closely related clusters. In each cluster the only phenotypic character that differed among strains was the O antigen, which might suggest that the genetic background for the LPS side chains can be transferred horizontally among EPEC strains. The results support the idea that O:H serotyping is useful for studies of epidemiologic linkages between cases of EPEC diarrhea.

Bacterial Adhesion↗
PubMed1990

Clonal diversity and virulence factors in strains of Escherichia coli of the classic enteropathogenic serogroup O114.

Eighty-eight Escherichia coli strains of the enteropathogenic (EPEC) group O114 that were isolated from humans and animals in geographically different places and over more than 30 years were examined for virulence markers, O:H serotypes, and for electrophoretic types by multilocus enzyme electrophoresis. Four major genetically tightly related clusters of strains showed close correlation between electrophoretic types and other phenotypic characters. Cluster I contained 35 EPEC class II strains of serotypes O114:H9 and O114:H- and 5 enterotoxigenic E. coli belonging to O114:H21 and O114:H49. Clusters II and III comprised 36 O114:H4, O114:H32, and O114:H- strains; most were of doubtful pathogenicity except one Verotoxin-positive O114:H4 strain isolated from a human with diarrhea. Cluster IV contained 9 classic EPEC strains of serogroup O114:H2 that were characterized by localized adherence to HEp-2 cells and by the EPEC adherence factor.

Alleles↗
PubMed1990

Genetic relationships among strains of avian Escherichia coli associated with swollen-head syndrome.

Genetic diversity among 22 Escherichia coli strains isolated from chickens with swollen-head syndrome (SHS), an acute respiratory disease of domestic poultry, and 93 strains isolated from birds with colibacillosis was assessed on the basis of allelic variation at 20 enzyme-encoding loci detected by multilocus enzyme electrophoresis. SHS isolates from Spain and Canada were polymorphic at 14 loci and were classified into 19 multilocus genotypes, defining clones that differed on average at 34% of the loci. In most cases, SHS isolates of different clonal genotypes were distinct in O:H serotype and expressed different fimbrial antigens. Comparisons with 93 isolates obtained from birds with colibacillosis revealed enzyme polymorphisms at 17 of 20 loci, with an average of 3.5 alleles per locus. In the total sample, 56 clonal genotypes were distinguished, with 27 (23%) of the isolates belonging to one of three common clones. Both SHS and colibacillosis isolates were genetically diverse, with an average single-locus diversity of 0.36, indicating that a wide variety of naturally occurring bacterial clones is associated with these acute avian infections. Six previously defined groups of clones identified in diseased birds from the United States were represented in isolates from Spain, indicating that similar clones occur in widely separated geographic areas. In addition, one group of SHS isolates was closely related to a recognized widespread clone complex incriminated in human septicemia and meningitis. The results suggest that certain strains implicated in SHS infections belong to a clone complex whose members have special attributes that promote involvement in invasive diseases in humans and animals.

Alleles↗
PubMed1990

Genetic population structure, clonal phylogeny, and pathogenicity of Salmonella paratyphi B.

Genetic diversity and relationships among 123 strains of Salmonella paratyphi B (serotype 1,4,[5],12:b:[1,2]) were estimated from an assessment of electrophoretically demonstrable allelic variation at 24 chromosomal enzyme gene loci. Fourteen electrophoretic types, marking clones, were distinguished, the phylogeny of the clonal lineages was reconstructed, and biotype and other phenotypic characters were mapped onto this structure. Most d-tartrate-negative strains are members of an abundant, globally distributed clone (Pb 1) that is polymorphic for many biotype characters (including d-tartrate utilization), bacteriophage type, rRNA pattern, and colicin M and phage ES18 sensitivity. This clone is largely responsible for S. paratyphi B enteric fever in humans. In contrast, d-tartrate-positive strains (formerly known as S. java) occurred in all seven of the clonal lineages identified by population genetic analysis, although most d-tartrate-positive isolates belong to only two clones (Pb 3 and Pb 4), which vary in frequency geographically. Monophasic strains represent four closely related clones forming a distinctive phylogenetic lineage. The Kauffmann hypothesis of convergence in serotype among distantly related cell lineages through recombination (via phage transduction or other means) may account for the considerable genotypic diversity among clones of S. paratyphi B. Pb 4, Pb 6, and Pb 7 are more closely allied with clones of S. typhimurium and S. saintpaul than with other clones of S. paratyphi B. Sensitivity or resistance to colicin M and phage ES18 and the electrophoretic pattern of the rRNA, which were incorporated into a recently proposed scheme for the identification of types of S. paratyphi B, individually or in combination fail to mark clones or other meaningful phylogenetic subdivisions.

Colicins↗
PubMed1990

Phylogenetic distribution of branched RNA-linked multicopy single-stranded DNA among natural isolates of Escherichia coli.

Multicopy single-stranded DNA (msDNA), a branched DNA-RNA molecule, has been shown in Escherichia coli B and clinical strain Cl-1 to be synthesized by reverse transcriptase. We report that 13% of the strains of the ECOR collection, a sample of 72 E. coli isolates representing the breadth of genetic variation of the species, produce msDNA. Three of the four major subspecific groups include msDNA-producing strains. Screening of 25 isolates that are genetically related to msDNA-producing clinical strains uncovered 22 additional msDNA-producing strains. A phylogenetic tree based on allelic variation detected electrophoretically at 20 enzyme-encoding loci revealed two major clusters and several deep branches composed of strains that synthesize msDNA. Although E. coli K-12 does not harbor msDNA, other closely related strains of the K-12 family do. The results support the hypothesis that msDNA-synthesizing systems, including reverse transcriptase genes, were acquired recently and independently in different lineages of E. coli.

Animals↗
PubMed1989

Genetic relationships among Escherichia coli isolates causing urinary tract infections in humans and animals.

Genetic variation in isolates of Escherichia coli obtained mostly from urinary tract infections in humans and domesticated animals (dogs and cats) was assessed for 16 enzymes using multilocus enzyme electrophoresis to characterize chromosomal genotypes. A total of 148 isolates comprised 63 distinct electrophoretic types (ETs) and about half of the isolates belonged to one of 9 common ETs. A bootstrap analysis of genetic distance between ETs revealed three significant groups of strains. Variation in allele frequencies among groups accounted for 40% of the total genetic diversity. The majority of the common ETs fell into a major cluster of closely related strains. The recovery of multiple isolates of the same electrophoretic types and serotypes from unassociated hosts suggests that these bacteria represent uropathogenic clones that are widely disseminated in humans and animals.

Animals↗
PubMed1988

Genetic evidence of clonal descent of Escherichia coli O157:H7 associated with hemorrhagic colitis and hemolytic uremic syndrome.

Genetic relatedness of 100 strains of Escherichia coli, isolated mostly from patients with hemorrhagic colitis or hemolytic uremic syndrome, was determined for chromosomal genotypes on the basis of allelic variation at 17 enzyme-encoding loci detected by multilocus enzyme electrophoresis. Fifteen of the 17 loci were polymorphic, with an average of 3.5 alleles per locus. Comparison of the observed combinations of alleles among strains revealed 25 distinct multilocus genotypes, which were used to define naturally occurring cell lineages or clones. Cluster analysis of the genotypic data revealed that isolates of serotype O157:H7 fall into a well-defined group of clonal genotypes that share alleles, on average, at 90% of their enzyme loci. The O157:H7 clonal group is only distantly related to other Verotoxin-producing strains belonging to other serotypes of E. coli. The results strongly support the hypothesis that isolates of E. coli O157:H7 obtained from geographically separate outbreaks and sporadic cases of hemorrhagic colitis and hemolytic uremic syndrome belong to a pathogenic clone that occurs throughout North America.

Alleles↗
PubMed1988

Genetic relationships among pathogenic strains of avian Escherichia coli.

Genetic relationships among 79 strains of Escherichia coli, isolated mostly from diseased chickens, were estimated on the basis of allelic variation at 15 enzyme-encoding loci, determined by multilocus enzyme electrophoresis. All 15 loci were polymorphic, with an average of 4.1 allelic states per locus. Comparisons of the observed combinations of alleles among strains revealed 37 distinct multilocus genotypes that were used to define naturally occurring cell lineages or clones. Two-thirds of the isolates were classified into 10 clones, including a single multilocus genotype that accounted for about a third of all isolates. For isolates of these clones, there was a high concordance (76%) between identity in multilocus genotype, O:K:H serotype, and pattern of resistance to five antibiotics. Cluster analysis disclosed two major complexes of closely related clones, in which more than 50% of the isolates were associated with localized infections (airsacculitis and pericarditis). Both complexes contained isolates with serotype O2:K1, indicating that this serotype can occur on diverse chromosomal backgrounds. The results suggest that colibacillosis within avian populations is caused by a relatively limited number of pathogenic clones representing at least two distinct clone complexes.

Alleles↗
PubMed1988

Genetic relationships among pathogenic Escherichia coli of serogroup O157.

Escherichia coli strains of serotype O157:H7 are a newly described clonal pathogenic form associated with recent outbreaks of hemorrhagic colitis in humans. Although O157 strains of various H types have long been recognized as enterotoxigenic in animals, little is known about how these pathogenic animal strains are related to those of serotype O157:H7. To determine the genetic relatedness of O157:H7 isolates to animal O157 strains, we examined 194 O157 isolates, representing 12 distinct flagellar antigens (H serotypes), obtained from a variety of animal and human infections. To characterize isolates, we assayed allelic variation at 19 enzyme loci by multilocus enzyme electrophoresis. Genotypic comparisons of isolates revealed extensive variation among 33 distinct clonal genotypes that differed, on average, at 44% of the enzyme loci. K88 fimbriae were expressed in 72% of the isolates and occurred in a diversity of chromosomal genotypic backgrounds. Five major clonal groups were recognized; one group was clearly associated with porcine colibacillosis, and another was associated with human urinary tract infections. The O157:H7 genotype was not closely allied with any of the major groups of clones. The results indicate that O157 E. coli are genetically diverse and strongly suggest that the O157:H7 lineage was not recently derived from other pathogenic strains of the O157 serogroup.

Alleles↗
PubMed1987

Genetic relationships and clonal population structure of serotype 2 strains of Neisseria meningitidis.

Two hundred and thirty-four strains of Neisseria meningitidis, including 94 serotype 2a, 111 serotype 2b, and 19 serotype 2c isolates, together with 10 isolates that were serotyped as 2 with polyvalent antiserum but did not react with monoclonal antibodies, were characterized by the electrophoretic mobilities of 15 metabolic enzymes. Of these enzymes, 14 were polymorphic, and 56 distinctive combinations of alleles at the enzyme loci (electrophoretic types) were identified, among which the mean genetic diversity per locus was 0.413, or about 75% of that recorded for the species N. meningitidis as a whole. Mean genetic diversity among electrophoretic types of the same serotype (2a, 2b, or 2c) was, however, on average, less than half the total species diversity, and no multilocus genotypes were shared between isolates of the different serotypes, which belong to distinctive clonal lineages. Recent temporal changes in the frequencies of recovery of pathogenic strains of serotypes 2a and 2b in South Africa and North America resulted from clone replacement in these populations rather than evolutionary modification of the serotype protein of the initially dominant clones.

Genetic Variation↗
PubMed1987

Genetic relationships among the oral streptococci.

Genetic relationships and species limits among the oral streptococci were determined by an analysis of electrophoretically demonstrable variation in 16 metabolic enzymes. Fifty isolates represented 40 electrophoretic types, among which the mean genetic diversity per locus was 0.857. Mannitol-1-phosphate dehydrogenase was not detected in isolates of the sanguis species complex, and glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were absent in species of the mutans complex. Clustering from a matrix of Gower's coefficient of genetic similarity placed the 40 electrophoretic types in 10 well-defined groups corresponding to the Streptococcus species S. mutans, S. sobrinus, S. cricetus, S. rattus, S. ferus, S. oralis (mitior), two distinct assemblages of S. sanguis strains, and two subdivisions of "S. milleri." The assignments of isolates to these groups were the same as those indicated by DNA hybridization experiments, and the coefficient of correlation between genetic distance estimated by multilocus enzyme electrophoresis and genetic similarity indexed by DNA hybridization was -0.897 (P less than 0.001) for 50 pairwise combinations of isolates. S. ferus, which is widely believed to be a member of the mutans complex, was shown to be phylogenetically closer to species of the sanguis complex.

Animals↗