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PubMed1986

Antitumor and immunologic effects of a pyridine-extracted fraction of Propionibacterium acnes.

The antitumor and immunological effects of a pyridine extractable fraction of Propionibacterium acnes were tested in a murine ovarian teratocarcinoma (MOT) model. Previous studies have demonstrated that tumor rejection in this model depends upon sequential activation of tumoricidal neutrophils (PMNs) followed by cytostatic macrophages. The pyridine extract significantly prolonged the survival of mice challenged with 10(3) or 10(4) MOT cells but had little impact on a 10(5) tumor inoculum. In vivo cytoreduction occurred within the first 24 h following IP treatment which correlated temporally with the influx of tumoricidal PMNs into the peritoneal cavity. Immunotherapy failure in mice challenged with 10(5) MOT cells occurred between 48 and 72 h after treatment when macrophage chemotaxis into the peritoneal cavity was initiated. Although injection of unfractionated bacteria activated MOT-cytostatic macrophages, the pyridine extract was deficient in this regard. Intraperitoneal injection of the pyridine extract resulted in an early (day +1) depression and late (day +5) enhancement of peritoneal NK cytotoxicity. These data suggest that the retention of neutrophil-activating moieties in the pyridine extract are sufficient for antitumor effects against low tumor inocula while the depletion of macrophage-activating determinants results in diminished effects against larger tumor cell challenges.

Adjuvants, Immunologic↗
PubMed1983

A 2.5-year follow-up of local immunotherapy of advanced stomach and intestinal adenocarcinoma with Propionibacterium granulosum.

Intratumoral injections of 10 mg cells walls from Propionibacterium granulosum strain KP-45 (PG) were applied in 14 patients with advanced, metastatic stomach (five cases) and colorectal (nine cases) adenocarcinoma. Each patient had his own "twin" control. All patients received no other anticancer treatment, except analgetics and/or palliative surgery. Treatment with PG resulted in partial regression of tumors accompanied by improvement of the clinical state of these patients as well as the reappearance of normal values in blood count biochemical parameters. In each pair of twin cases, survival of the PG-treated patient was longer than the untreated control. The mean survival of PG-treated patients was 23.5 months (4 of 14 patients being still alive after 2.5 years follow-up), while all control patients died with a mean survival period of 6.4 months. The difference between these two patient groups of about 17 months is significant (p greater than 0.01).

Adenocarcinoma↗
PubMed1976

Lactate metabolism in Propionibacterium pentosaceum growing with nitrate or oxygen as hydrogen acceptor.

When anaerobic cultures of Propionibacterium pentosaceum were shifted to low dissolved-oxygen concentration (D.O.C.), acetate production from lactate diminished and propionate production stopped, whereas pyruvate accumulated and oxygen was consumed. Assuming that energy is generated in the electron transfer to oxygen, YATP values (g dry wt bacteria/mole ATP) of between 7.2 and 11.9 were calculated from molar growth yields and product formation. When oxidative phosphorylation in the electron transfer to oxygen was ignored, unreasonably high YATP values were obtained. From these results it is concluded that energy is indeed generated in the electron transfer to oxygen. However, synthesis of cytochrome b was strongly repressed by oxygen. Furthermore, synthesis of all catabolic enzymes studied was impaired in bacteria growing at low D.O.C. Thus, the anaerobic character of P. pentosaceum may be explained by the inhibition of synthesis of both cytochrome b and enzymes in the presence of oxygen. It was demonstrated that nitrate reductase is synthesized constitutively in P. pentosaceum. Synthesis of nitrate reductase was stimulated by nitrate and repressed by oxygen. Synthesis of fumarate reductase was also repressed by oxygen, whereas only a small effect of nitrate on this enzyme was observed. However, propionate formation is inhibited during growth with nitrate. The absence of propionate formation in the presence of oxygen and nitrate is explained by inavailability of NADH needed for the conversion of oxaloacetate into malate in the reductive pathway to succinate, so that succinate and propionate cannot be formed.

Acetates↗
PubMed1979

Studies on Propionibacterium isolated from paddy soils.

The anaerobic bacteria occurring in paddy soils sampled from fields belonging to the Rice Research Station at Ohmagari in Akita Prefecture, Japan, were surveyed from May to November, 1974. Irregularly shaped rods predominated which were found to be gram-positive, strictly anaerobic, catalase-positive and not heat-resistant; populations were estimated at 10(5)--10(-7) cells/g dry soil throughout the entire survey period. On the basis of their morphological and physiological characteristics these bacteria were identified as Propionibacterium. Most strains belonged to P. lymphophilum and P. granulosum.

Anaerobiosis↗
PubMed1985

Isolation of an acidic polysaccharide antigen from Propionibacterium acnes.

An acidic polysaccharide antigen is released from Propionibacterium acnes I and II during growth. The molecular weight of the antigen was heterogeneous and when fractionated on a Sepharose CL-6B column, the antigen was detected at Kav values of between 0.1 and 1.0. The pI of the antigen was below 3.5. Rabbit antiserum raised against purified acidic-polysaccharide agglutinated P. acnes showing that the polysaccharide was a surface antigen. Human antibodies towards whole P. acnes-II organisms were quantitated by an agglutination technique, and antibodies towards purified acidic polysaccharide were quantitated by single radial immunodiffusion. A high prevalence of antibodies against whole bacteria and the acidic polysaccharide was found in sera from healthy individuals. The antibody titre in sera from acne patients was significantly higher than that in sera from blood donors.

Acne Vulgaris↗
PubMed1980

Antibodies against extractable components from Propionibacterium acnes in humans with and without acne vulgaris.

Acidic polysaccharides (AP) are released from Propionibacterium acnes I and II during growth. Similar antigens are released from two strains of P. avidum, but in a smaller amount. Furthermore, prostaglandin-like substances (PLS) have been isolated from the lipid fraction of P. acnes. The AP antigens give rise to a precipitation reaction against a large proportion of normal sera. However, significantly higher antibody titre levels towards the AP fraction were found in patients with severe acne vulgaris. No rise of antibodies was found towards PLS. These findings suggest that AP's may contribute to the inflammatory response in acne vulgaris as antigens, whereas PLS, as one of the potential mediators trigger development of the initial lesions.

Acne Vulgaris↗
PubMed1980

The in vivo cytostatic effect induced by Propionibacterium granulosum on murine tumor cells.

The cytostatic action of Propionibacterium granulosum was studied in a mouse sarcoma in vivo. Kinetic analysis of tumor cells 28 days after tumor implantation and systemic immunotherapy showed that the cell cycle time was identical in both treated and untreated tumors. P. granulosum treatment resulted in a marked prolongation of the S phase and shortening of the G1 phase of the cell cycle. A pronounced drop in the number of labeled interphases and the reduction of the growth fraction were observed in tumors obtained from mice given injection of P. granulosum. Cloning efficiency of tumor cells from P. granulosum treated animals was quantitatively similar to that of control animals and only differences in the size of lung colonies were observed.

Animals↗
PubMed1984

Influence of pH on porphyrin production in Propionibacterium acnes.

Propionibacterium acnes was grown on Eagle's medium for 4-15 days at pH 5.3-7.2 The porphyrin production was measured both by direct fluorometry and by high pressure liquid chromatography (HPLC). The greatest concentration of porphyrins was produced at pH 6.1. Protoporphyrin was the dominant porphyrin species present in the bacteria in all samples. The relative amount of coproporphyrin was greatest at pH 6.7 after 4 days of incubation. In human skin there are local variations in the pH; therefore our findings may be of importance for porphyrin production in acne.

Chromatography, High Pressure Liquid↗
PubMed1983

Multiple forms of cytochrome b in the electron transport system of Propionibacterium shermanii.

Membrane particles from Propionibacterium shermanii contain cytochromes b and d as the major cytochrome components. Potentiometric titration of the membranes indicate two distinct groups of b-type cytochromes differing in their midpoint potentials by at least 100 mV. Low temperature spectra of redox-poised membranes show that the high potential group consists of two components with approximate lambda max and midpoint potentials as follows: cytochrome b562-563 (+120 mV); cytochrome bHP556-557 (+90 mV). Resolution of the low potential group of b-type cytochromes is less clear cut but there appear to be two further components with different lambda max values but very similar midpoint potentials: cytochrome bLP556-557 (-20 mV) and cytochrome b553-554 (-20 mV). Cytochrome d630 titrates as a single species with an approximate midpoint potential of +140 mV. The low potential pair of b-type cytochromes have midpoint potentials sufficiently low to permit their functioning as components of the anaerobic electron transport path to fumarate while the high potential pair of b-type cytochromes and cytochrome d probably function on an aerobic branch of the electron transport pathway. The characteristics of the aerobic and anaerobic steady-state spectra are largely consistent with these suggestions.

Cell Membrane↗
PubMed1975

The electron transport system of the anaerobic Propionibacterium shermanii: cytochrome and inhibitor studies.

1. Electron transport particles obtained from cell-free extracts of Propionibacterium shermanii by centrifugation at 105000 times g for 3 hrs oxidized NADH, D,L-lactate, L-glycerol-3-phosphate and succinate with oxygen and, except for succinate, with fumarate, too. 2. Spectral investigation of the electron transport particles revealed the presence of cytochromes b, d and o, and traces of cytochrome alpha1 and a c-type cytochrome. Cytochrome b was reduced by succinate to about 50%, and by NADH, lactate or glycerol-3-phosphate to 80--90%. 3. The inhibitory effects of amytal and rotenone on NADH oxidation, but not on the oxidation of the other substrates, indicated the presence of the NADH dehydrogenase complex, or "site I region", in the electron transport system of P. shermanii. 4. NQNO inhibited substrate oxidations by oxygen and fumarate, as well as equilibration of the flavoproteins of the substrate dehydrogenases by way of menaquinone. The inhibition occurred at low concentrations of the inhibitor and reached 80--100%, depending on the substrate tested. The site of inhibition of the respiratory activity was located between menaquinone and cytochrome b. In addition, inhibition of flavoprotein equilibration suggested that NQNO acted upon the electron transfer directed from menaquinol towards the acceptor to be reduced, either cytochrome b or the flavoproteins, which would include fumarate reductase. 5. In NQNO-inhibited particles, cytochrome b was not oxidized by oxygen-free fumarate, but readily oxidized by oxygen. It was concluded from this and the above evidence that the branching-point of the electron transport chain towards fumarate reductase was located at the menaquinone in P. shermanii. It was further concluded that all cytochromes were situated in the oxygen-linked branch of the chain, which formed a dead end of the system under anaerobic conditions. 6. Antimycin A inhibited only oxygen-linked reactions of the particles to about 50% at high concentrations of the inhibitor. Inhibitors of terminal oxidases were inactive, except for carbon monoxide.

Aerobiosis↗
PubMed1982

Effect of 13-cis-retinoic acid on sebum production and Propionibacterium acnes in severe nodulocystic acne.

Ten patients treated with 13-cis-retinoic acid demonstrated a 70% reduction in sebum excretion on the forehead and cheek. An average reduction of 66% occurred in the 1st month, slowly increased to 70% by the 3rd month, and then remained constant for the final 2 months of therapy. Concomitant with this sebum excretion reduction was a fall in the number of Propionibacterium acnes recovered from both sites. Pretreatment values of 10(4) P. acnes per square centimeter (cm2) fell to 10(3) per cm2 after 1 month and 10(2) after 9 months of therapy. P. acnes was not recovered from six of the ten subjects in the following 3 months and only at levels of 10(2) per cm2 in three subjects. One subject's P. acnes level was reduced to only 10(4) per cm2. Following discontinuation of therapy, sebum levels and P. acnes counts showed a trend to recover to pretreatment levels within 2 months.

Acne Vulgaris↗
PubMed1980

Aerobic electron transport in Propionibacterium shermanii. Effects of cyanide.

Cyanide inhibited D- and L-lactate and NADH oxidase activities of membrane particles from Propionibacterium shermanii but only at relatively high concentrations. Inhibition occurred at two different sites in the electron transport pathway. One site, with a half-maximal inhibition concentration (I0.5) of 2 to 3 mM KCN, is located at the terminal oxidase involved in cytochrome b oxidation; the evidence is consistent with cytochrome d being the major oxidase involved. At high concentrations, cyanide inhibited reduction of cytochrome b by D-lactate (I0.5 value 20-25 mM cyanide). A proportion of the oxygen-uptake remained uninhibited even by 100 mM cyanide; this proportion was about 80% for succinate, 30% for L-lactate, 15% for D-lactate and 10% for NADH. The oxygen uptake per mol of substrate oxidised increased with increasing cyanide concentration and was accompanied by the formation of hydrogen peroxide as a product of a cyanide-insensitive oxidase system.

Aerobiosis↗
PubMed1981

Activation of the alternative pathway of complement in human serum by Propionibacterium acnes (Corynebacterium parvum) cell fractions.

Activation of the alternative pathway of complement is known to be initiated by bacterial structures. We have fractionated Propionibacterium acnes cells, purified various cell fractions, and tested their complement-activating ability in human serum chelated with ethyleneglycol bis-(beta-aminoethylether)-N,N1-tetraacetic acid. The majority of complement-activating activity was localized in the wall fraction. This activity was resistant to lipid extraction, protease, RNAse, DNAse and lysozyme treatment. NaIO4, formamide, and hot (but not cold) trichloroacetic acid (TCA) extraction ablated the complement-activating capacity of cell walls. Compounds removed by extraction failed to consume significant hemolytic activity against antibody-coated sheep erythrocytes (EA). Addition of TCA-extracted soluble material to cell wall suspensions resulted in an inhibition of hemolytic consumption by the cell wall. These results indicate that, in P. acnes, complement-activating molecules are located in the cell wall and are carbohydrate in nature. Peptidoglycan, lipid, protein, and nucleic acid do not appear to contribute to the cell wall's ability to activate complement.

Carbohydrates↗
PubMed1980

Characterization of serum-independent polymorphonuclear leukocyte chemotactic factors produced by Propionibacterium acnes.

The size and production of polymorphonuclear leukocyte (PMN) chemotactic factors by Propionibacterium acnes has been studied. All eight strains of P. acnes which were tested liberated PMN chemotactic factors in their growth culture media. The factor(s) produced by one strain, 6919, were studied in greater depth. The PMN response was proportional to the dose of culture supernatant and chemotactic activity increased with the duration of P. acnes culture. The neutrophil migration towards culture supernatants was chemotactic, with a slight stimulation of random migration by 72-h supernatants. The size of the chemotactic molecules was studied through dialysis, ultrafiltration, and Sephadex G-25 chromatography of 72-h supernatants. Low-molecular-weight chemotactic factors were found to be predominant by each method of size determination.

Chemotactic Factors↗
PubMed1979

Propionibacterium acnes pneumonia in a patient with lymphoma.

A 57 year-old male with lymphocytic lymphoma developed symptoms of cough, fever and progressive dyspnea accompanied by a diffuse lower lung infiltrate. Open lung biopsy revealed multiple micro-abscesses surrounding small bronchioles which yielded a pure growth of Propionibacterium acnes.

Biopsy↗
PubMedDate not supplied

Culture and biological activity of Propionibacterium acnes.

Administration of killed Propionibacterium acnes to experimental animals leads to the development of hypersensitivity to the lethal and cytokine-inducing effects of endotoxin. This sensitizing property of P. acnes is not always expressed by different bacterial preparations. Its expression depends very much on the conditions employed for the cultivation of this microorganism. The present study investigates which culturing conditions result in P. acnes preparations with optimal sensitizing properties. The composition of the medium, the culturing time and temperature as well as the type of cultivation (in minifermentor or stationary culture) were all varied for this purpose. The resulting bacterial preparations were killed at 65 degrees C for 1 h and tested for sensitizing activity. The results show that stationary cultures of P. acnes grown at 37 degrees C for 4 to 5 days in the appropriate medium produce biologically active preparations with satisfactory sensitizing activity.

Animals↗
PubMedDate not supplied

Shunt nephritis associated with Propionibacterium acnes.

Membranoproliferative glomerulonephritis was observed in a 22-year-old male patient in whom a ventriculoatrial shunt and a ventricular catheter were implanted after he was diagnosed in September 1989 with a cerebral cyst. Propionibacterium acnes infection of a central nervous system shunt was diagnosed. The ventriculoatrial shunt was removed (the catheter had become embedded in tissue and was left in place) and the patient was treated with cefotaxime (3 x 2 g) for 14 days. Renal function improved, but recovery was not complete.

Adult↗
PubMed1985

Small-cell lung cancer and immunochemotherapy with Propionibacterium granulosum KP 45.

Seventy-nine patients with small-cell lung cancer were treated with vincristin, methotrexate, and cyclophosphamide in inductive therapy and with methotrexate, cyclophosphamide, and procarbazine in maintenance therapy. Patients were divided at random into two groups: one group received chemotherapy alone and the second group was additionally subjected to systemic immunotherapy with Propionibacterium granulosum strain KP-45. In general, differences in the frequency of therapy response and in duration of remission could not be stated between the two groups of patients, but patients responding to chemotherapy showed a significantly longer remission time and lower complication rates. This benificial effect of chemoimmunotherapy is not related to a direct antitumor activity of the immunomodifier used, but to the lowered risk of myelosuppression and infections. Immunomodulation in combination with chemo- and/or radiotherapy can be recommended for the treatment of small-cell lung cancer.

Adult↗