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R K Selander

Publications and source records attributed to R K Selander.

At least 109 records · Page 6Linked to original sources

Genetic relationships of serologically nontypable and serotype b strains of Haemophilus influenzae.

A collection of 242 strains of Haemophilus influenzae, including 65 nontypable (unencapsulated) isolates and 177 encapsulated serotype b isolates recovered largely from children with invasive and noninvasive diseases in the United States, was characterized by the electrophoretic mobilities of 15 metabolic enzymes presumably encoded by chromosomal genes. All enzymes were polymorphic for three to seven electromorphs, and 94 distinctive multilocus genotypes (electrophoretic types [ETs]) were distinguished, among which mean genetic (allelic) diversity was 0.500. Isolates recovered from cases of invasive or noninvasive diseases did not differ significantly in level of genetic variation. The observation that 29 ETs were represented exclusively by serotype b isolates and that each of the 65 nontypable isolates was of a unique ET strongly confirmed the hypothesis that unencapsulated clinical isolates are not merely phenotypic variants of the common serotype b cell lines. Rather, the two types of isolates are distinctive subsets of the multilocus chromosomal genotypes of the species as a whole. Serotype b capsule occurred in three groups of isolates that are distantly related in multilocus enzyme genotype. Isolates of four closely related nontypable biotype IV ETs associated with obstetrical infections or neonatal bacteremia were highly divergent from all others examined and may be specifically distinct. A phylogenetic scenario was proposed in which the ancestor of H. influenzae was encapsulated and the nontypable clones arose by convergent evolutionary loss of the ability to synthesize or extracellularly express a polysaccharide capsule.

Alleles↗

Genetic relationships and clonal structure of strains of Escherichia coli causing neonatal septicemia and meningitis.

Genetic diversity and relationships among 63 isolates of Escherichia coli from infants in Finland with septicemia or meningitis were assessed by analyzing electrophoretic variation in 21 enzymes encoded by chromosomal genes. Thirty-nine multilocus genotypes (electrophoretic types) were distinguished, 23 of which formed a closely related, distinctive subset (group 1) of five or six clones represented by 40 (63%) of the isolates. The remaining isolates represented a second subset of 16 electrophoretic types (group 2) that were, on the average, rather more distantly related to one another. Although the number of electrophoretic types causing neonatal systemic disease is smaller than that occurring in healthy intestinal floras, the pathogenic electrophoretic types are only slightly less diverse genetically. Isolates of group 1 were characterized by relatively high incidences of hemolysin production and S, type 1, type 1C, and P fimbriae. However, because phenotypic characters, considered individually or in combination, did not adequately reflect the overall genetic relationships of isolates, it is recommended that the genetic structure of populations be defined on the basis of multilocus chromosomal genotypes.

Escherichia coli↗

Genetic diversity and relationships in populations of Bordetella spp.

Genetic diversity in 60 strains of three nominal Bordetella species recovered from humans and other mammalian hosts was assessed by analyzing electrophoretically demonstrable allelic variation at structural genes encoding 15 enzymes. Eleven of the loci were polymorphic, and 14 distinctive electrophoretic types, representing multilocus genotypes, were identified. The population structure of Bordetella spp. is clonal, and genetic diversity is relatively limited compared with most other pathogenic bacteria and is insufficient to justify recognition of three species. All isolates of Bordetella parapertussis were of one electrophoretic type, which was closely similar to 9 of the 10 electrophoretic types represented by isolates of Bordetella bronchiseptica. Bordetella pertussis 18-323, which is used in mouse potency tests of vaccines, is more similar genetically to isolates of B. bronchiseptica and B. parapertussis than to other isolates currently assigned to the species B. pertussis. Apart from strain 18-323, the isolates of B. pertussis represented only two closely related clones, and all isolates of B. pertussis from North America (except strain 18-323) were genotypically identical. Strain Dejong, which has been classified as B. bronchiseptica, was strongly differentiated from all of the other Bordetella isolates examined.

Alleles↗

Paleoepidemiologic investigation of Legionnaires disease at Wadsworth Veterans Administration Hospital by using three typing methods for comparison of legionellae from clinical and environmental sources.

Multilocus enzyme electrophoresis, monoclonal antibody typing for Legionella pneumophila serogroup 1, and plasmid analysis were used to type 89 L. pneumophila strains isolated from nosocomial cases of Legionnaires disease at the Veterans Administration Wadsworth Medical Center (VAWMC) and from the hospital environment. Twelve L. pneumophila clinical isolates, obtained from patients at non-VAWMC hospitals, were also typed by the same methods to determine typing specificity. Seventy-nine percent of 33 VAWMC L. pneumophila serogroup 1 clinical isolates and 70% of 23 environmental isolates were found in only one of the five monoclonal subgroups. Similar clustering was found for the other two typing methods, with excellent correlation between all methods. Enzyme electrophoretic typing divided the isolates into the greatest number of distinct groups, resulting in the identification of 10 different L. pneumophila types and 5 types not belonging to L. pneumophila, which probably constitute an undescribed Legionella species; 7 clinical and 34 environmental VAWMC isolates and 2 non-VAWMC clinical isolates were found to be members of the new species. Twelve different plasmid patterns were found; 95% of VAWMC clinical isolates contained plasmids. Major VAWMC epidemic-bacterial types were common in the hospital potable-water distribution system and cooling towers. Strains of L. pneumophila which persisted after disinfection of contaminated environmental sites were of a different type from the prechlorination strains. All three typing methods were useful in the epidemiologic analysis of the VAWMC outbreak.

Antibodies, Monoclonal↗

A population genetic framework for the study of invasive diseases caused by serotype b strains of Haemophilus influenzae.

One hundred seventy-seven isolates of serotype b Haemophilus influenzae recovered largely from children with invasive disease in the United States were characterized by the electrophoretic mobilities of 16 metabolic enzymes, the NaDodSO4/PAGE pattern of outer-membrane proteins (OMP), and biotype. Thirty-two distinctive multilocus genotypes (electrophoretic types, ETs) were distinguished on the basis of allele profiles at the enzyme loci. Twenty-eight OMP types and five biotypes were identified, but only 55 distinctive combinations of ET, OMP type, and biotype were represented. The strong nonrandom associations of characters and the recovery of isolates with identical properties in widely separated geographic regions and over a 40-year period suggest that the population structure of H. influenzae is basically clonal. Examination of nonserotype b isolates indicated that clones of serotype b are a restricted subset of the genotypes in the species as a whole. Currently, most of the invasive H. influenzae disease in the United States is caused by serotype b strains of two related ETs, and, more specifically, much of it is attributable to two subclones marked by OMP type. There is evidence that the frequency of the ET-1/OMP 1H/biotype I subclone has increased dramatically in the United States since the 1939-1954 period. The hypothesis that populations of H. influenzae are subject to marked temporal variation in clonal composition is supported by evidence of major differences in the genetic structure of populations in the United States and the Netherlands.

Bacterial Outer Membrane Proteins↗

Genetic diversity in relation to serotype in Escherichia coli.

The extent of chromosomal-gene diversity among 261 isolates of Escherichia coli sharing single O, K, or H antigens and various combinations thereof was estimated by multilocus enzyme electrophoresis, which detects allelic variation in structural genes. The results of this study indicate that the genetic diversity among isolates sharing single antigenic determinants can approach or equal that observed among randomly chosen strains; that the magnitude of the diversity varies among antigens; and that the genetic diversity is reduced, but not eliminated, among isolates sharing two antigenic determinants. With one exception, isolates of the same O:K:H serotype were of identical or closely related electrophoretic types (ETs). Isolates of the same ET generally shared the same combination of antigenic determinants, but some ETs included isolates of different serotypes. The implications of these findings for epidemiological research and the clone hypothesis of population structure are discussed, and possible evolutionary mechanisms causing antigenic divergence and convergence are considered.

Antigens, Bacterial↗

Genetic structure of populations of Legionella pneumophila.

The genetic structure of populations of Legionella pneumophila was defined by an analysis of electrophoretically demonstrable allelic variation at structural genes encoding 22 enzymes in 292 isolates from clinical and environmental sources. Nineteen of the loci were polymorphic, and 62 distinctive electrophoretic types (ETs), representing multilocus genotypes, were identified. Principal coordinates and clustering analyses demonstrated that isolates received as L. pneumophila were a heterogeneous array of genotypes that included two previously undescribed species. For 50 ETs of L. pneumophila (strict sense), mean genetic diversity per locus was 0.312, and diversity was equivalent in ETs represented by isolates recovered from clinical sources and those collected from environmental sources. Cluster analysis revealed four major groups or lineages of ETs in L. pneumophila. Genetic diversity among ETs of the same serotype was, on average, 93% of that in the total sample of ETs. Isolates marked by particular patterns of reactivity to a panel of nine monoclonal antibodies were also genetically heterogeneous, mean diversity within patterns being about 75% of the total. Both Pontiac fever and the pneumonic form of legionellosis may be caused by isolates of the same ET. The genetic structure of L. pneumophila is clonal, and many clones apparently are worldwide in distribution. The fact that L. pneumophila is only 60% as variable as Escherichia coli raises the possibility that isolates recovered from clinical cases and man-made environments are a restricted subset of all clones in the species as a whole.

Alleles↗

Distribution of multilocus genotypes of Escherichia coli within and between host families.

Isolates from the intestinal Escherichia coli flora of 28 members of five families (including parents, children, and household pets) in Amherst, Massachusetts, and Rochester, New York, were characterized by the electrophoretic mobilities of 12 enzymes to estimate the extent of sharing of strains among associated and unassociated hosts. Among the 655 isolates examined, 60 different combinations of electromorphs (electrophoretic types or ETs), each representing a distinctive multilocus genotype, were identified, of which 85% were recovered from only a single individual. On average, 11% of the ETs isolated from the same family were shared by two or more members; 4.9% of ETs were shared among members of unassociated families living in the same city; and only 2% were shared by families in different cities. All three ETs that were recovered from multiple hosts in the present study are widespread clones that have been isolated from many other host individuals in North America and Sweden.

Animals↗

Evidence for clonal population structure in Escherichia coli.

Genotypes of 142 K1 isolates of four O serogroups of Escherichia coli from human hosts in Europe and the United States were characterized by an electrophoretic analysis of allozymic variation in 12 chromosomally encoded enzymes. The genetic structure of natural populations revealed by this analysis is closely similar to that indicated in earlier studies by Achtman and colleagues of the electrophoretic migration pattern for four outer membrane proteins and the chemical structure of the cell-wall lipopolysaccharides. The combined evidence demonstrates that most of the K1 isolates belong to a small number of geographically widespread clones. The distribution of O serogroups among the isolates does not consistently correspond to the clonal structure; O1:K1 isolates represent at least two distantly related, geographically widespread clones, one of which is genetically similar to a clone of the O18:K1 serotype. These findings for K1 isolates add to a growing body of evidence supporting the hypothesis that the genetic structure of natural populations of E. coli is basically clonal, with very limited recombination of chromosomal genes. Clonal structure has important implications for the study of the determinants of pathogenicity and disease specificity in E. coli.

Cloning, Molecular↗

Standard reference strains of Escherichia coli from natural populations.

A set of 72 reference strains of Escherichia coli isolated from a variety of hosts and geographical locations has been established for use in studies of variation and genetic structure in natural populations. The strains, which have been characterized by multilocus enzyme electrophoresis, are representative of the range of genotypic variation in the species as a whole.

Animals↗

Association of infection caused by Pseudomonas aeruginosa serotype O11 with intravenous abuse of pentazocine mixed with tripelennamine.

From July 1979 to June 1983, 25 of 40 intravenous drug addicts with systemic infections had Pseudomonas aeruginosa as the etiological agent; by 1982, P. aeruginosa had replaced Staphylococcus aureus as the most common pathogen. At least 21 of the 25 addicts with P. aeruginosa infection abused pentazocine mixed with tripelennamine (commonly known as T's and blues) compared with 6 of 15 addicts infected with other pathogens (P = 0.006). Of the 25 P. aeruginosa isolates, 23 were of serotype O11. Phenotypic patterns in isolates from addicts and in 22 serotype O11 control isolates from nonaddicts were determined by pyocin and electrophoretic enzyme typing, as well as by susceptibility to heavy metals and antibiotics. Of 25 isolates from addicts, 20 were identical or differed by only one marker, whereas the 22 nonaddict serotype O11 isolates were distributed among 17 distinct phenotypic patterns. We postulate that the emergence of P. aeruginosa as the major cause of deep infection in addicts is a consequence of contamination of their paraphernalia during preparation of pentazocine and tripelennamine for self-injection. The phenotypic similarity among isolates from addicts may reflect acquisition from related environmental sources and an unusual ability of certain serotype O11 strains to survive preparation of the drugs or to be invasive.

Drug Contamination↗

Molecular area effects in Cepaea.

Enzyme polymorphisms in the land snail Cepaea nemoralis in the central Pyrenees show concordant geographic patterns of strong differentiation that are not correlated with the distributions of characters of shell color and banding or with the major pattern of variation in climate and vegetation type. Three regions of relative genetic uniformity separated by steep clines in allele frequencies are designated as "molecular area effects." A model of allopatric differentiation of populations in temporary geographic isolation during the last period of Pleistocene glaciation, followed by invasion of the Pyrenees and hybridization in secondary contact, is proposed to account for the present-day pattern of genetic differentiation. The genetic structure of the Pyrenean populations of C. nemoralis is not interpretable in terms of stasipatric or parapatric models of speciation.

Journal Article↗

Multilocus genetic structure in natural populations of Escherichia coli.

A survey of allozyme variation at 12 enzyme loci in 1,705 clones of the genetic species Escherichia coli (including four species of Shigella) from natural populations revealed 302 unique allele combinations (electrophoretic types). Single-locus diversity estimates fall within the range predicted by the neutral allele theory of molecular evolution, but the combination of alleles in electrophoretic types are highly nonrandom, as indicated by a test of association over all loci and by evidence of complex linkage disequilibria in several four-locus combinations. These linkage disequilibria reflect genetic differentiation of E. coli into three groups of strains. Because of restricted recombination, both the stochastic extinction of lines and selective differences between particular genetic combinations may have contributed to the evolution of subspecific structure in E. coli.

Electrophoresis↗

Geographic components of linkage disequilibrium in natural populations of Escherichia coli.

Geographic variation in the genetic structure of natural enteric populations of Escherichia coli was assessed at both the single-locus and dilocus levels from allozyme genotypes at 12 enzyme loci in 178 cell lines isolated from human hosts in Sweden, Iowa, and Tonga. Although there was significant heterogeneity in allele frequencies at six of the 12 loci, geographic variation accounted for only 2.0% of the total genetic diversity (HT = 0.518). Ohta's D-statistics were used to partition the total variance of dilocus linkage disequilibrium into within-population and between-population components. The observed total variance in disequilibrium (0.0339), averaged over 66 locus-pairs, was significantly greater than would be expected (0.0103) if alleles were randomly associated in an unstructured total population; and both within-locality and between-locality components made substantial contributions to the total variance. Half the locus-pairs exhibited the specific dual relationship among components expected when random factors are generating disequilibrium, but 20% of the locus-pairs showed the opposite relationship, reflecting systematic allele associations. The magnitude of dilocus disequilibrium apparently is unrelated to the chromosomal distance between loci. This and other evidence indicates that substitutive recombination rates in natural populations are sufficiently low to permit indirect periodic selection to play a prominent role in generating multilocus genetic structure.

Escherichia coli↗

Enzyme polymorphism and genetic population structure in Escherichia coli and Shigella.

Electrophoretically demonstrable variation in 12 enzymes was studied in more than 1 600 isolates of Escherichia coli from human and animal sources and in 123 strains of the four species of Shigella. All 12 enzymes were polymorphic; and the number of allozymes (mobility variants), which were equated with alleles, averaged 9.3 per locus in E. coli. For Shigella species, the mean number of alleles was 2.9 per locus. Some 77% of the allozymes recorded in Shigella were shared with E. coli. A total of 302 unique genotypic combinations of alleles over the 12 loci (electrophoretic types, ETs) was distinguished, of which 279 represented E. coli and 23 were Shigella. Among electrophoretic types, mean allelic diversity per locus was 0.52 for E. coli and 0.29 for Shigella. It was estimated that there are, on the average, about 0.3 detectable codon differences per locus between pairs of strains of E. coli and Shigella, which is roughly equivalent to 1.2 amino acid differences per enzyme. Evidence that the enzyme loci studied are a random sample of the genome is provided by a significant positive correlation between estimates of genetic divergence between pairs of strains obtained by DNA reassociation tests and estimates of genetic distance between the same strains based on electrophoresis. A principal components analysis of allozyme profiles revealed that the 302 ETs fall into three overlapping clusters, reflecting strong non-random associations of alleles, largely at four loci. Each of the four ETs of E. coli that have been most frequently recovered from natural populations has an allozyme profile that is very similar to, or identical with, the hypothetical modal ET of one of the groups. ETs of Shigella fall into two of the groups. No biological significance can at present bbe attributed to the genetic structure revealed by Multilocus electrophoretic techniques. The electrophoretic data are fully compatible with other molecular and more conventional evidence of a close affinity between E. coli and Shigella, and they raise questions regarding the present assignments of certain strains to species. In support of evidence from DNA reassociation tests and serotyping, the present study suggests that S. sonnei is homogeneous in chromosomal genotype.

Adult↗