Bacteriophages as an efficient therapy for antibiotic-resistant septicemia in man.
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Bacterial Infections↗
Biomedical subjects
M Mulczyk
Publications and source records attributed to M Mulczyk.
[Current clinical application of bacteriophages and perspectives for their genetic modifications].
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Bacterial Infections↗
Effective phage therapy is associated with normalization of cytokine production by blood cell cultures.
The aim of this study was to investigate the effect of phagotherapy on tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) serum levels and the ability of blood cells to produce these cytokines in culture. Fifty one patients with long-term, suppurative infections of various tissues and organs were enrolled. The ability of cells to secrete cytokines was tested using whole blood cell cultures, unstimulated or stimulated with lipopolysaccharide (LPS) from E. coli. In addition, cytokine serum levels were determined. Measurement of cytokine activity was performed using bioassays. We showed that TNF-alpha, but not IL-6 serum levels, were regulated upon division of patients into categories exhibiting initial: low, moderate and high cytokine levels. The low spontaneous production of IL-6 by blood cell cultures was elevated significantly on day 21 of phage therapy, whereas high release of this cytokine was inhibited. No such correlation was observed with LPS-induced IL-6 production in cell cultures when cells from low-, moderately- or highly-reactive patients were studied. Phage therapy modified TNF release according to the initial ability to produce that cytokine: it reduced TNF production in high responders and increased it in low responders. Patients infected only with Gram-positive bacteria demonstrated analogous changes in the spontaneous and LPS-induced TNF-alpha production as in the whole studied group. A similar kind of regulation was observed in TNF-alpha and LPS-induced production, i.e. low production was significantly elevated, high strongly inhibited, and moderate only slightly affected. In summary, we demonstrated for the first time that effective phage therapy can normalize TNF-alpha serum levels and the production of TNF-alpha and IL-6 by blood cell cultures.
Bacterial Infections↗
Bacteriophage therapy of bacterial infections: an update of our institute's experience.
1307 patients with suppurative bacterial infections caused by multidrug-resistant bacteria of different species were treated with specific bacteriophages (BP). BP therapy was highly effective; full recovery was noted in 1123 cases (85.9%). In 134 cases (10.9%) transient improvement was observed and only in 50 cases (3.8%) was BP treatment found to be ineffective. The results confirm the high effectiveness of BP therapy in combating bacterial infections which do not respond to treatment with the available antibiotics.
Bacterial Infections↗
[The study on biology of bacteriophages and their usage in the treatment of bacterial diseases and on the influence of different bacteriophages on cytokine production by leukocytes in human peripheral blood].
The authors showed the examinations of the biology bacteriophages and using them in the treatment of the bacteriology infection and influence difference bacteriophages in producing cytokinins by leukocytes of human peripheral blood.
Bacteriophages↗
Effect of outer membrane proteins (OMP) of Shigella on interleukin 2 (IL-2) production by spleen cells of mice.
The kinetics of interleukin (IL-2) release from mouse spleen cells incubated with different doses of outer membrane proteins (OMP) from Shigella was investigated. OMP induced very low activity of IL-2 after 2 and 4 h, and only a slightly higher level of the cytokine was detected after 6 h. However, IL-2 activity increased markedly after 20 and 24 h of incubation, and doses of 5 and 10 micrograms of OMP were found to be the most effective. Spleen cells cultured with OMP for 48 h contained reduced concentration of IL-2.
Animals↗
[Studies of humoral immunity induced by proteins of the cell wall of Hafnia alvei].
It was found that cell wall proteins (CWP) of Hafnia alvei applied intraperitoneally to mice are inducing, beside previously detected cellular immunity, also humoral immunity. Applying ELISA immunoenzymatic test in which a conjugate enabling demonstration of IgG antibodies was applied, it was found that CWP of Hafnia alvei induce appearance of specific antibodies in a high titer, but their presence in mouse serum is short and independent from applied doses of CWP. Humoral immunity induced by CWP can be transferred passively to nonimmunized animals by application of high level immune serum, which protected fully the animals against infection with homological strains of Hafnia alvei even in dilution 1:100. Investigated serum did not exhibit protective activity against infection with heterological strains of Hafnia alvei.
Animals↗
Induction of tumor necrosis factor and interleukin 6 by outer membrane proteins of Shigella in spleen cells and macrophages of mice.
The ability of outer membrane proteins (OMP) of Shigella flexneri to induce tumor necrosis factor (TNF) and interleukin 6 (IL-6) production by spleen cells and macrophages of mice was investigated. Treatment of spleen cells with OMP resulted in the release of only traces of TNF activity. In contrast, macrophages treated with OMP produced moderate levels of TNF. OMP was also found to be an inducer of IL-6. Both spleen cells and macrophages, treated with OMP, were found to produce substantial levels of this cytokine. The effect of OMP on the release of TNF and IL-6 was dose and time dependent, maximal production being reached at 10 micrograms of OMP after 20 h. The ability of OMP to induce production of these cytokines may explain part of the previously described immunomodulatory effects of this preparation on the immune system.
Animals↗
Studies on immunity in mice immunized with outer membrane proteins of Hafnia.
Nonspecific protection induced in mice after administration outer membrane proteins of Hafnia alvei against infection with homologous and heterologous bacteria was transferred into other mice with lymphocytes isolated from spleens of mice immunized with outer membrane proteins. It was also found that mice sensitized with outer membrane proteins derived from H. alvei or with living bacteria induced in animals delayed hypersensitivity (DTH) in homologous and heterologous systems. The observed type of hypersensitivity was transferable to normal mice by lymphocytes obtained from donor animals which were previously sensitized with OMP. The experiments revealed that immunity induced with outer membrane proteins of Hafnia alvei is cell-mediated.
Animals↗
Some biological properties of outer membrane proteins of Hafnia.
Outer membrane proteins (OMP) isolated from four antigenically different strains of Hafnia alvei were tested for the toxicity, pyrogenicity, ability to induce Shwartzman reaction as well as for their influence on the leukocyte system. LD50 doses for the studied preparations determined on inbred mice were 18, 20, 28 and 34 mg/kg. These differences in the toxicity of the preparations were reflected in manifestation of Shwartzman reaction; more toxic preparations induced strongest necrohemorrhagic changes at the site of injection. The OMP preparations injected intravenously to rabbits caused moderate increase of body temperature. They induced changes in the number of leukocytes in the animals comparable with those of other preparates of bacterial origin.
Animals↗
Effect of outer membrane proteins from Shigella on humoral immunity induced in mice by SRBC.
Shigella flexneri outer membrane proteins (OMP) which had been earlier found to exert immunomodulatory effect on cell mediated immune response were also found to act as immunomodulator of the humoral immune response. Effects of OMP were investigated in the experiments in vitro and in vivo, where the level of humoral immune response, measured as the number of plaque-forming cells (PFC) to SRBC in the spleen was evaluated. We demonstrate that small doses of OMP (1-5 micrograms) stimulate, whereas higher doses (10-50 micrograms) suppress the humoral immunity.
Adjuvants, Immunologic↗
Fraction of spleen cells responsible for suppression of cellular immune response to SRBC in mice treated with outer membrane proteins of Shigella.
Effect of splenocytes isolated from mice immunized with suppressive dose of OMP from Shigella on delayed hypersensitivity, induced in mice with sheep red blood cells was investigated. Only the population of T lymphocytes was found to suppress the delayed hypersensitivity, as measured by the footpad reaction. The results suggest that OMP of Shigella are able to induce in the spleens of animals active T cells which are responsible for the suppression of cellular response induced by SRBC.
Animals↗
Humoral response in mice immunized with outer membrane proteins of Hafnia alvei. Protective activity of anti-OMP-antibodies.
Intraperitoneal immunization of mice with outer membrane proteins (OMP) of Hafnia alvei induced in the animals a synthesis of specific antibodies. The antibody levels, determined by ELISA test, were found to be relatively low in the sera of mice immunized with a single dose (5 micrograms) of OMP and after a second immunization. However, they were higher in mice immunized with three doses of OMP. The antibodies were present in circulation for a relatively short time after immunization. Serum containing anti-OMP antibodies given intraperitoneally to normal mice protected them only against challenge with a homologous Hafnia strain.
Animals↗
Studies on nonspecific protection induced with OMP of Shigella flexneri and other genera of Enterobacteriaceae.
Outer membrane proteins (OMP) isolated from Shigella flexneri, Escherichia coli, Proteus vulgaris and Salmonella typhimurium were tested for their protective activity. Each OMP preparate given to mice intraperitoneally in a single injection (5 micrograms/per mouse) protected the animals not only in homologous but also in varying intensity in heterologous systems. Evidence was obtained that this nonspecific protection is cell mediated.
Animals↗
Immunogenic and protective properties of outer membrane proteins of Hafnia alvei.
Outer membrane proteins (OMP) extracted from antigenically distinct or related strains of Hafnia alvei containing defined composition of major proteins proved to be immunogenic. Intraperitoneal immunization of mice with a single dose of such preparations protected the animals against homologous and heterologous Hafnia strains. The OMP preparations were also found to induce protection with varying intensity against Escherichia, Proteus, Shigella and Salmonella.
Animals↗
Genetic and molecular characterization of pR351 plasmid from enteropathogenic Escherichia coli strain.
A pR351 plasmid (Tc Ap Cb) conferring drug resistance of naturally occurring E. coli strain was examined. Conjugation and transduction experiments have indicated that this plasmid is R plasmid aggregate consisting of three independent plasmids: a) conjugative plasmid pR351 A (SuTc) fi- (F) belonging to incompatibility group L, b) conjugative plasmid pR351 B (SuApCb) fi- (F) belonging to incompatibility O, and c) non-conjugative plasmid pR351 C (ApCb). The existance of these plasmids in pR351 plasmid aggregate was confirmed by the agarose gel analysis of plasmid DNA isolated from the lysates of E. coli J53 transconjugants carrying pR351 A or pR351 B plasmids and from E. coli K12 C600 transductant carrying pR351 C plasmid. Molecular mass of these plasmids was found to be 55.60 and 3 Mdal respectively. The non-conjugative pR351 C plasmid could be mobilized by Col B and F factors. Our findings have indicated that two fi- (F) R plasmids can stably coexist in R plasmid aggregate.
Drug Resistance, Microbial↗
Hafnia alvei lipopolysaccharides: isolation, sugar composition and SDS-PAGE analysis.
Lipopolysaccharides (LPS) of 33 strains of Hafnia alvei were isolated and purified. LPS content of the dry bacterial mass ranged from 1.2 to 4.5%. All examined lipopolysaccharides contained glucose, glucosamine, heptose, 3-deoxy-octulosonic acid and often galactose. Rhamnose, mannose, galactosamine, mannosamine and unidentified amino sugars were found in some H. alvei strains. Sialic acid was present in LPS of one strain. D-3-Hydroxybutyryl groups also were identified in lipopolysaccharides of 5 strains of this genus. SDS-PAGE of the lipopolysaccharides was presented in the paper. According to these results two core types exist in H. alvei.
Carbohydrates↗
Phagocytic and bactericidal properties of macrophages of mice immunized with outer membrane proteins (OMP) of Shigella.
Macrophages obtained from peritoneal exudates of mice immunized with the single doses (1 and 5 micrograms) of OMP were shown to have stronger phagocytic as well as bactericidal properties in relation to Shigella flexneri bacilli than nonactivated macrophages. Macrophages from the animals immunized with 10, 20 and 30 micrograms OMP doses showed phagocytic and bactericidal properties similar to those of nonactivated macrophages while the immunization with the dose 50 micrograms resulted in their suppression. Likewise, activity of macrophages from mice immunized twice or three times with various doses of OMP did not differ much from that obtained after immunization with single OMP doses. On the other hand, immunization of mice with a sublethal dose of live Shigella flexneri did not activate either phagocytic or bactericidal properties of macrophages. Besides, phagocytic and bactericidal activity of macrophages of mice immunized with OMP of Shigella was determined in relation to Salmonella typhimurium. The doses 1 and 5 micrograms of OMP resulted in slight activation of macrophages which manifested itself by a little increase in their phagocytic and bactericidal ability. When used in the dose 10 micrograms, OMP remained without any effect on the above activity of macrophages. Only the dose 50 micrograms, slightly suppressed their phagocytic properties.
Animals↗