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Biomedical subjects

K Linde

Publications and source records attributed to K Linde.

At least 91 records · Page 5Linked to original sources
PubMed1990

Modulating the microbial colonization of the gastrointestinal tract by oral administration of defined Escherichia coli strains. I. Influencing the biotope by means of metabolic drift mutants of Escherichia coli.

Through the selection of spontaneous metabolic drift mutants (selection marker RifR) of an Escherichia coli strain (O6:H2 SmR) of known settling capacity in conventional mice, it was attempted to obtain clones with positively optimized in vitro characteristics, which may exert a promotive influence upon the in vivo colonizing behaviour. Using 512 drift mutant strains (E. coli O6:H2 SmR RifR) we were able to establish positive optimizations, at an over-aleatory rate, for each of the in vitro characters tested (haemagglutination capacity of rabbit, guinea pig, and fowl erythrocytes; overgrowing power of mouse-adapted wild-type E. coli strains; formation of biomass with exclusive utilization of dextrose, lactose, fructose, adonitol, salicin, rhamnose, mannose; multiplying power; quantitative motility; and capacity to synthesize mucus). A higher settling rate (larger number of animals in which the test strain shared greater than or equal to 50% of the Enterobacteriaceae population than that obtained with the initial strain) could be established for one out of the 62 clones tested in vivo (a rise from 20% to 55%). The higher settling rate was associated with combinations of various functional parameters and not with an improvement of any of the individual functions. Despite the increase in settling rate relative to the number of experimental animals used in these studies, it was not generally possible to obtain a more than 3 days' dominance of the test strain within the lac+ Enterobacteriaceae. This is considered to be due primarily to the incipient synthesis of secretory IgA.

Administration, Oral↗
PubMed1990

Modulating the microbial colonization of the gastrointestinal tract by oral administration of defined Escherichia coli strains. II. Influencing the biotope by means of geographically unrelated Escherichia coli strains.

An effective increase in the rate of colonization can be accomplished, in analogy with the pathogenetic mechanism of what is known as travelers' disease, through the administration of geographically unrelated strains. As compared to Escherichia coli strains isolated in the GDR, metabolic drift-optimized and Ethiopian strains showed an increase from 20 to 50%. It was not, however, possible to maintain a greater than or equal to 50% share in the population of Enterobacteriaceae over a period of more than up to three days. Immunologic mechanisms are considered to be responsible for this.

Administration, Oral↗
PubMed1988

Local and systemic immune response in rabbits after intraintestinal immunization with a double-marker attenuated strain of Salmonella typhimurium.

Local and systemic immune response was studied in 3 groups of rabbits immunized and reimmunized 190 days later with S. typhimurium double-marker attenuated strain 1,771 and doses ranged from 20.10(9) to 0.2.10(9) cells. Another group of rabbits was immunized with extract (hydroxylammine) vaccine. It was found that the attenuated strain persisted for considerable time in the gut, and induced pronounced and continuous immune response as measured by the passive hemagglutination test. The serum antibody response had the character of a secondary one with switching on the synthesis of IgM to IgG already after basic immunisation. By the Coombs' technique it was shown that specific immunoglobulins demonstrated in feces were secretory antibodies of the class IgA (SIgA). The immune response developed after reimmunization was still more vigorous and prolonged pointing to an immune memory existance. It was possible to obtain well manifested immunity with the lowest dose. The extract vaccine revealed only weak and transitory serum and intestinal antibody levels without SIgA appearance. The results obtained in this setup make S. typhimurium 1771 a perspective candidate for a live vaccine.

Animals↗
PubMed1987

Technological investigations with attenuated strains of Shigella for production of live vaccines. 1. Cultivation in a fermenter of an attenuated strain S. flexneri 2a with two markers.

A method was developed for cultivation of the strain Shigella flexneri 2a 77 with two attenuated markers. It ensures the preservation of the initial properties of the strain. The regimen for control of dissolved oxygen level was optimized. It was established that yeast extract is a necessary component of the nutritive medium used. The role of the phase and quantity of the inoculum for growth of the bacterial population has been clarified. Fresh fermenter culture, applied in rats, shows a high immunogenic activity. After lyophilization, the cultures retain 50-70% of the immunogenic activity of the non-lyophilized cultures. The method makes preconditions for the production of a live attenuated dysentery vaccine for oral administration.

Animals↗
PubMed1983

Stable, highly immunogenic mutants of "Salmonella" with two independent, attenuating markers as potential live vaccine and their validity for "Shigella" and other bacteria.

This paper presents for Salmonella sp. an easily realizable principle to develop high-immunogenic, stable live vaccines with two independent attenuating mutations, which is valid for Shigella sp. and Pasteurella s. too. To avoid overattenuation by the stepwise introduction of two attenuating markers, only those mutations are suitable which do not suppress pathogenic structures or essential metabolic functions, but only transduce them into a leaky function, as e.g.: mutagen induced auxotrophic phenotypes with diminished virulence by commutation; purine dependent strains, which hitherto erroneously were regarded as non-immunogenic and particularly distinct chromosomal resistant genotypes, in which the conformational change of the drug target simultaneously causes resistance and changes virulence behaviour (pathwaydrift-mutants). Moreover, in Salmonella, an additional high sensitivity marker against ten sides and drugs possessing a permeation barrier in the outer membrane diminishes--without influence on virulence and immunogenicity--surviving in intestine (bile) and (detergent contaminated) environment. Therefore this hst-marker confers antiepidemic quality to vaccine strains and increases safety. To meet security demands for such vaccines with laboratory methods some easy and practicable tests for standardization are suggested, which include estimation of reversion frequency of pur- and hst marker and the proof of immunogenicity for mice. The safety and efficacy of such vaccine strains are pointed out by veterinarians in live-stock.

Animals↗
PubMed1981

[High-immunogenic mutants of Salmonella with two independently of each other attenuating markers as potential vaccines from bacteria capable of multiplication. I. communication: usefulness of the purin-auxotrophy for the isolation of high-immunogenic and stable double-marker strains (author's transl)].

The Salmonella example demonstrates a principle for the isolation of high-immunogenic, stable Salmonella-mutants with two independently of each other attenuating mutations as potential vaccines from bacteria capable of multiplication. The isolation of such double-marker vaccination-strains is verified by the treatment of a single-marker strain (for instance an attenuated high-immunogenic auxotrophic pheno-type) with mutagen and the following selection of clones with the marker purin-auxotrophy as a second attenuating mutation. The demonstrated double-marker strains S. typhimurium his-155 pur-4 and S. dublin met-91 pur-23 are designated by the following parameters: Stability under the conditions of the practical vaccine application; immunogenicity for mice by one immunization only, and separability from homologous wild strains with simple laboratory methods.

Animals↗
PubMed1981

[High-immunogenic mutants of Salmonella with two independently of each other attenuating markers as potential vaccines from bacteria capable of multiplication. 2. Communication: spontaneous chromosomal resistance against antibiotics as a possibility for isolation of clones with decreased virulence (author's transl)].

Mutants of Salmonella typhimurium with spontaneous chromosomal resistance against oleandomycin, streptothricin, nalidixic acid and rifampicin were investigated for their virulence behaviour with the i.p. mouse model. The strains resistant against the special antibiotic consists of a spectrum of various clones with a different behaviour of virulence: Additionally to obvious unchanged virulent strains there are such with a weak or strong attenuation. The majority of the attenuated strains protect the immunized mice against a following lethal wild strain infection. High-immunogenic attenuated double-marker mutants for application as potential vaccine strains may be isolated with the aid of a step by step introduction of a second attenuating "resistance"-marker in a one-marker strain, attenuated for another reason. These strains show the following parameters: -stability under the conditions of practical vaccine application, because a simultaneous back-mutation in both attenuating markers by reason of the unrealizable germ numbers will not occur, -immunogenicity by one immunization only, -separation from homologous wild strains of another origin with simple laboratory methods. This obvious generally acting biological principle is explained on the basis of molecular biological considerations and by referring to the literature. A test for orientation using an attenuated RNA-polymerase mutant showed, the resistance against rifampicin and attenuation are transferred together by co-transduction.

Animals↗
PubMed1980

[Preparation of stable Salmonella vaccine strains through combination of 2 independently attenuating markers with no limitation on growth].

Attenuation by only one single marker with no limitation on propagation (frequency of backmutation being less than 10(-7) will not provide sufficient safety against complications along with vaccination. (This notion, derived from both theoretical considerations and practical experience, does not rule out good stability of certain one-marker mutants under practice conditions.) Two independently attenuating markers with no limitation on propagation, however, do ensure full stability on account of potentiating single frequencies of backmutation (less than 10(-14)). The second attenuating marker must be measurable, and it must not be allowed to bring about substantive reduction in the one-marker mutant's immunogenicity. The following principle was conceptualised for the purpose of resolving the problem: A pool of attenuated highly immunogenic mutants with one single marker without limitation on propagation was rendered available, such as an S-form auxotrophic set of phenotypes (attenuation by co-mutation) or R-form mutants with the potential of tissue persistence. An attenuated second marker then was rendered available which was highly immunogenic as a "one-marker mutant", for example, mutants with adenine (purine) dependence with attenuation a pleiotropic effect and limited availability of metabolities. The second marker was introduced in a one-maker mutant, with verification of additional attenuation along with remaining immunogenicity. The following results were obtained: --Experimental parameters for attenuation and immunogenicity in mice: one single intraperitoneal immunisation, using 10(5), 10(6), 10(7), and 10(8) mutant germs; challenge on 20th day from intraperitoneal immunsation with about 100 LD50; lethality of controls 95 per cent or more; --S. typhimurium his-155/ade-4 and S. dublin met-91/ade-23: LD50: 10(8) germs; Immunogenicity: 90 per cent or more survived exposure to wild strain; --S. cholerae-suis R Dessau/ade-4: LD50: about 10(9) germs; immunogenicity: about 50 per cent only within endotoxic limits, about 10(8) germs or more; --S. typhimurium his-155/marker 2 (enzyme mutation): LD50 about 10(8) germs; immunogenicity: 90 per cent or more survived exposure to wild strain.

Adenine↗
PubMed1978

[Use of attenuated mutants of Pasteurella multocida strain, pathogenic to calves, in experimental mouse model studies. 4. Immunogenicity of selected revertants of temperature-sensitive, streptomycin-dependent mutants as potential vaccine strains].

Temperature-resistant or streptomycin-independent revertants were isolated from temperature-sensitive or streptomycin-dependent mutants of a Pasteurella multocida strain with pathogenicity to calf. The revertants were tested for virulence in mice and for their immunogenicity against wild-strain infection, using 100 times and more of the lethal dose. The following conclusions may be derived from the results thus obtained: 1. Most of the fully attenuated streptomycin-independent revertants failed to provide sufficient protection against wild-strain infection, following one single intraperitoneal immunization. 2. Selected streptomycin-independent revertants protect about 60% of mice immunized with one single intraperitoneal less than or approximately LD10 germ count dose, and 100% of mice immunized two times against lethal challenge. 3. Selected temperature-resistant revertants produced high immunity in mice, with one single intraperitoneally less than or approximately LD10 germ count dose protecting roughly 95 per cent of all animals against lethal infection. 4. The temperature-resistant revertant 9 b/1 and 9 b/5 and the streptomycin-independent revertant 1/14 are on the agenda as potential vaccine strains which can provide full or sufficient protection on the basis of one single immunization.

Animals↗