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D A Caugant

Publications and source records attributed to D A Caugant.

124 records · Page 7Linked to original sources
PubMed1987

Intercontinental spread of Neisseria meningitidis clones of the ET-5 complex.

The genetic structure of populations of Neisseria meningitidis was examined by an analysis of electrophoretically demonstrable allelic variation at 15 structural genes encoding enzymes in 688 isolates. Variation among strains in serogroup and serotype has little relationship to the complex structure of populations revealed by enzyme electrophoresis, which involves 14 major lineages of clones diverging from one another at more than half their genetic loci. Clones of one of these lineages, the ET-5 complex, have been identified as the causative agent of recent outbreaks and epidemics of meningococcal disease in Europe, South Africa, Latin America, and the United States. There is evidence that organisms of the ET-5 complex reached Florida via human immigrants from Cuba.

Cuba↗
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 structure of Neisseria meningitidis populations in relation to serogroup, serotype, and outer membrane protein pattern.

The genetic structure of populations of Neisseria meningitidis was examined by an analysis of electrophoretically demonstrable allelic variation at 15 genes encoding enzymes in 650 isolates of eight serogroups (A, B, C, W135, X, Y, Z, and 29E) and 38 nonserogroupable isolates. A total of 331 distinctive multilocus genotypes (electrophoretic types, ETs) was identified, among which mean genetic diversity per locus (H = 0.547) was greater than in Escherichia coli and other bacterial species thus far studied. The intercontinental distribution of some ETs and the recovery of organisms of identical genotype over periods of many years strongly suggest that the genetic structure of N. meningitidis is basically clonal as a consequence of low rates of recombination of chromosomal genes. Variation among strains in serogroup, serotype, and the electrophoretic pattern of the major outer membrane proteins has little relationship to the complex structure of populations revealed by enzyme electrophoresis, which involves 14 major lineages of clones diverging from one another at genetic distances greater than 0.50. Genetic diversity among ETs of isolates of the same serogroup was, on average, 84% of that in the total sample. Clones of serogroup A were unusual in being genotypically less heterogeneous than those of other serogroups and in forming a single phylogenetic group. Isolates of the same serotype or outer membrane protein pattern were also highly heterogeneous; on average, 87 and 97%, respectively, of the total species diversity was represented by ETs of the same serotype or outer membrane protein.

Bacterial Outer Membrane Proteins↗
PubMed1986

Intercontinental spread of a genetically distinctive complex of clones of Neisseria meningitidis causing epidemic disease.

Strains of Neisseria meningitidis responsible for an epidemic of meningococcal disease occurring in Norway since the mid-1970s and for recent increases in the incidence of disease in several other parts of Europe have been identified by multilocus enzyme electrophoresis as members of a distinctive group of 22 closely related clones (the ET-5 complex). Clones of this complex have also colonized South Africa, Chile, Cuba, and Florida, where they have been identified as the causative agents of recent outbreaks of meningococcal disease. There is strong circumstantial evidence that outbreaks of disease occurring in Miami in 1981 and 1982 were caused in large part by bacteria that reached Florida via human immigrants from Cuba.

Disease Outbreaks↗
PubMed1986

Multilocus genotypes determined by enzyme electrophoresis of Neisseria meningitidis isolated from patients with systemic disease and from healthy carriers.

Variation in nine enzymes in 152 isolates of Neisseria meningitidis from Norway (118 from blood or cerebrospinal fluid of patients with systemic disease and 34 from the pharynx of healthy carriers) was analysed by starch-gel electrophoresis. All nine enzymes were polymorphic and the number of allozymes (electromorphs) identified per locus ranged from 3 to 12, with a mean of 6.1. Among the 152 isolates, 55 unique combinations of electromorphs (electrophoretic types, ETs) were distinguished. Twenty ETs were represented among the carrier isolates and 37 among the systemic isolates; hence, only two ETs were found in both groups of isolates. ET-5 was identified 67 times among the 118 systemic isolates (58%), indicating an association of this ET with invasiveness; ET-5 was also the most common type among the carrier isolates (18%). Genetic similarity between ETs was analysed by pairwise comparison of all 55 ETs with respect to the number of electromorphs by which they differed. No evidence of a general genetic difference between carrier and case isolates was found. Two well-defined clusters of ETs were observed, each including one of the two most common ETs identified among the systemic isolates (ET-5 and ET-37), together with isolates differing from them only at one or two loci. All isolates of ET-5 and ET-37, as well as their closely related variants defined by the similarity matrix, were resistant to sulphonamide, independent of their antigenic characteristics and isolation site. The extensive allozyme variation among isolates of the same serogroup demonstrated the limited value of serogrouping as an epidemiological tool. All but one isolate of serotype 15:P1.16 were electrophoretically similar, as were all the 2a:P1.2 isolates. The 15:P1.15 isolates, however, were genetically heterogeneous. The distribution of alleles in genotypes identified among the systemic isolates indicated that genetic recombination may occur in natural populations of N. meningitidis.

Aconitate Hydratase↗
PubMed1986

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↗
PubMed1986

Application of multilocus enzyme gel electrophoresis to Haemophilus influenzae.

Multilocus enzyme electrophoresis was adapted to the study of Haemophilus influenzae. Protein extracts from sonicated whole bacteria were subjected to starch gel electrophoresis. After staining with substrates, the position of each isoenzyme (electromorph) was registered. Each isolate was assigned an electrophoretic type (ET) by the combination of electromorphs for the enzymes stained. Twenty-seven enzymes were tested; 12 were expressed in H. influenzae. Six enzymes were selected for subsequent study: malate dehydrogenase (MDH), phenylalanylleucine peptidase (PE2), 6-phosphogluconate dehydrogenase (6PG), adenylate kinase (AK), glucose 6-phosphate dehydrogenase (G6P), and phosphoglucose isomerase (PGI). They were polymorphic and occurred in all isolates. Six electromorphs were found for PE2, G6P, and PGI, five for MDH, four for 6PG, and three for AK. PE2, G6P, and PGI contributed most of the ET resolution (48 of 49 ETs). Multilocus enzyme electrophoresis showed several advantages over previous typing techniques. An ET could be assigned to both typable and nontypable (NT) isolates. The technique was powerful in resolving differences among isolates. The 94 isolates comprised 49 ETs, five biotypes, and six capsular types and NT isolates. Strains known to be related expressed the same ET, e.g., RAB b+ and b-, ET12; Ma a+ and a-, ET1. ET variability among type b isolates was low; 26 of 28 clinical isolates expressed ET14; 2 of 28 expressed ET13 and ET15, differing from ET14 by one electromorph each. In contrast, the 47 NT isolates comprised 38 different ETs. No ETs were shared between non-type b capsulated strains and type b or NT strains. Interestingly, five NT isolates expressed the same ET as type b strains. (iv) Strains of the same capsular type but different biotypes expressed different ETs. ET determinations will thus be useful in studying the epidemiology and evolution of H. influenzae.

Bacterial Proteins↗
PubMed1986

Difference in structure between type b and nontypable Haemophilus influenzae populations.

The extent of chromosomal genetic variability and the genetic structure of Haemophilus influenzae populations was analyzed. A total of 119 isolates from humans in Göteborg, Sweden, and Birmingham, Ala., and 16 strains from a type culture collection were characterized for capsular type, biotype, outer membrane protein profile, and enzyme electrophoretic type (ET). The results of this study indicate that the bacteria identified as H. influenzae are a genetically extremely variable array of organisms. For the six enzymes studied, the estimated mean genetic diversity was 0.57 (approximately 20% higher than the corresponding estimate for Escherichia coli). Two lines of evidence indicate that despite its ability to recombine by transformation, H. influenzae maintains a largely clonal population structure. Although there is considerable potential for generating different genotypes, there were only 88 distinct ETs among the 135 strains, and isolates of the same ET and biotype were recovered at frequencies greater than would be anticipated at random. This evidence for a clonal population structure holds for uncapsulated as well as capsulated strains. However, these data also suggest that the stability of H. influenzae clones (clone persistence time) may be less than that of the nontransforming species E. coli. The ET data indicate that there is somewhat less variability among H. influenzae strains that express the same capsular antigens, biotype, and outer membrane proteins than among randomly chosen isolates. Nevertheless, there is substantial genetic variation among isolates within each of these classes and combinations thereof. There is also variation in these typing characteristics among strains of the same ET. These observations and those on genetic variability and population structures have implications for the characterization of H. influenzae isolates in clinical and epidemiological studies.

Bacterial Outer Membrane Proteins↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1981

Genetic diversity and temporal variation in the E. coli population of a human host.

Electrophoretic techniques were employed to study variation in chromosomal genes encoding enzymes and in the distribution of cryptic plasmids in the E. coli population of a human host over an 11-month period. Thirteen of the 15 enzymes studied were polymorphic, and mean genetic diversity per locus was 0.39. Among 550 clones isolated from fecal samples, protein electrophoresis revealed 53 distinct electrophoretic types (ETs). Most ETs appeared on only one or a few days and were considered transients, but two (ET-12 and ET-13) were observed many times over extended periods and represented residents. Complete turnover in the transient ETs in the population occurred in periods of from two weeks to a month. ETs appearing in one month showed no particular genetic similarity to those of the previous month. - All but 4 of the 53 ETs carried one or more "cryptic" plasmids with molecular weights ranging from 1 to 80 megadaltons. With few exceptions, the plasmid composition of each ET was unique. In the course of the 11-month sampling period, there were changes in the plasmid profiles of the resident strains ET-12 and ET-13, and also in the profile of a recurrent strain, ET-2, which was isolated on four days. Modification of the plasmid profile of ET-12 involved the sequential addition of relatively high molecular weight bands. For ET-2 and ET-13, the changes in the plasmid profiles were radical, suggesting invasions of new cell types rather than merely the addition and deletion of plasmids. - The results of this study provide three lines of evidence that recombination plays a minor role in the generation of genetic diversity in the E. coli population of a single host. (1) Several pairs of loci were in strong linkage disequilibrium; compared to a randomly generated array of genotypes, the sample of ETs contained an excess of pairs differing at one or two loci and too many pairs with highly distinctive combinations of electromorphs. (2) In most cases where pairs of ETs differed at a single locus and, therefore, could reasonably have been generated by phage- or plasmid-mobilized gene transfer, the plasmid profiles of the pair members were radically different and/or the potentially transmitted alleles were not present in other ETs in the population. (3) Although ET-12 was abundant, being represented by 252 of the 550 clones sampled, the electrophoretic type most similar to ET-12 different from it at six loci, and ET-12 carried two unique alleles. We conclude that most of the genetic diversity observed in this human host is a consequence of successive invasions of E. coli genotypes.

Alleles↗
PubMedDate not supplied

Meningitis outbreaks and vaccination strategy.

Three outbreaks of meningitis caused by Neisseria meningitidis serogroup A (subgroup III) are described: Niger (1991), Burundi (1992), and Guinea (1993). These outbreaks showed unusual characteristics: a shorter inter-epidemic interval (Niger), unusual geographical location outside the meningitis belt (Burundi and Guinea), and high age-specific attack rates in all age groups (Burundi and Guinea). Mass immunization campaigns mobilized considerable human and financial means (US $322,000 and 3000 person-days of work for health personnel to immunize 629,000 people in Guinea). The vaccination coverage was over 80% in densely populated areas (Burundi and urban Guinea), but below 50% in less populated areas (24/27 and 26/30 sub-districts in Niger and Guinea, respectively). The preventive fraction (proportion of cases prevented by vaccination) was substantial in Guinea (35% for a vaccine efficacy of 85%) and was higher where the campaign was initiated earlier. An 'alert' threshold indicating the onset of an epidemic of 15/100,000 cases in one week showed good sensitivity (94%), specificity (98%) and positive predictive value (89%) in Burundi, permitting quick decision making outside the meningitis belt. These 3 meningococcal meningitis outbreaks show the need for epidemic emergency preparedness and for vigilance on the whole African continent.

Adolescent↗