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PubMed1980

In vitro investigations on the action fosfomycin alone and in combination with other antibiotics on Pseudomonas aeruginosa and Serratia marcescens.

86.4% of the Pseudomonas aeruginosa and 91% of the Serratia marcescens strains were sensitive to fosfomycin. In combination with mezlocillin, cefoxitin, gentamicin and nalidixic acid a synergistic action was detected against these bacterial strains. It was most marked in the combination fosfomycin/nalidixic acid against Serratia marcescens. An acceleration of the fosfomycin action on the bacterial cells and the speed of bacteriolysis was observed in weakly acid medium (pH 6.0), in the presence of 10% active human serum and with increasing glucose-6-phosphate concentrations in the test medium. There is no parallel resistance between gentamicin and fosfomycin against Pseudomonas aeruginosa.

Anti-Bacterial Agents↗
PubMed1981

Quantitative differences between complement factor-B phenotypes.

In a study of 365 unrelated blood donors the structural polymorphism was determined by high-voltage electrophoresis followed by immunofixation with monospecific anti-Bf serum as described by Alper, Boenish & Watson (1972), and serum levels were measured by rocket-immunoelectrophoresis as described by Sjöholm (1975). We found that the mean level of Factor B in relation to structural phenotypes varies significantly in the order BfF greater than BfFS greater than BfS, though great variation was observed within types. A similar difference was also found with a functional assay of Factor B in agarose plates, although this method is less accurate. Concerning the biological functions, such as opsonization and bacteriolysis, it might be that individuals with the BfF allele are more able to withstand infectious agents than BfS subjects. The Bf polymorphism may therefore be transient, the BfF allele being in a process of replacing BfS by natural selection.

Alleles↗
PubMed1995

Proteinaceous precursors of human axillary odor: isolation of two novel odor-binding proteins.

The characteristic odor which arises in the human axillary region consists of volatile C6-C11 acids with the most abundant being (E)-3-methyl-2-hexenoic acid (E-3M2H). This acid, as well as several other components of the characteristic axillary odor, can be liberated from the odorless, aqueous soluble components of apocrine secretion by either saponification or bacteriolysis. It is therefore likely that a major characteristic odor is being carried to the skin surface bound to a water soluble precursor where it is liberated by axillary bacteria. The individual proteins found in apocrine secretions were separated, isolated and hydrolyzed with the resultant hydrolyzates analyzed by gas chromatography/mass spectrometry. These studies demonstrated that 3M2H was liberated from 2 proteins with apparent molecular mass of 26 and 45 kilodaltons: Apocrine Secretion Odor-Binding Protein 1 and 2, respectively (ASOB1 and ASOB2). Antisera to these proteins were prepared and used to examine a variety of other body fluids. Several fluids contained an immunoreactive protein with the same electropheretic migration pattern as the 45 KDa protein. Three of these body fluids (tears, nasal secretions and saliva) were separated into aqueous and organic soluble fractions and hydrolyzed to demonstrate that 3M2H could be liberated from the aqueous soluble materials. These results suggest interesting parallels between non-human mammalian odors used as chemical signals and human axillary odor. Previous studies have suggested the axillae as a source of human primer-type pheromones; consequently, if the odors which characterize the underarm are responsible for the pheromonal activity, then the chemistry involved may be similar to that in other mammalian chemical communication systems where proteins act as carriers of one or more chemical signals.

Adult↗
PubMed1975

Bactericidal activity of meningococcal antisera. Blocking by IgA of lytic antibody in human convalescent sera.

Humoral IgA, separated and purified from human sera drawn 12, 27, and 33 days after infection with serogroups B, Y, and C meningococci, respectively, has been shown to inhibit complement-mediated bacteriolysis by IgG and IgM purified from the same sera. Inhibition was dependent on the ratio of lytic to blocking antibody, was strain specific, and was greater for IgG than IgM. IgM was found to be more active than IgG in a bactericidal test. Activity of IgA appeared unrelated to the presence of a prozone in the whole serum. Similar inhibition was noted for IgA separated from rabbit sera.

Animals↗
PubMed1994

[Mechanisms of the intractability of bacterial infections in immunodeficiency status in childhood].

Most of the primary immunodeficiency diseases develop in childhood. The patients with antibody deficiency are susceptible to pyogenic bacteria since antibody is essential to opsonize bacteria. T cell deficiency causes defect of cytokine production needed to activate macrophages to kill intracellular bacteria such as mycobacteria and leeds to intractable infection of such bacteria. Complement mediated bacteriolysis is important to protect neisseria such as meningococcus and deficiency of C5-C9 provides susceptibility to the bacteria. Defect of superoxide synthesis or adhesion of neutrophils is related to severe infection of pyogenic bacteria. On the way of development of immune system, children especially in early infancy display susceptibility to bacterial infections.

Age Factors↗
PubMed1996

[In vitro and in vivo antibacterial activities of sulopenem, a new penem antibiotic].

The in vitro and in vivo antibacterial activities of sulopenem, a new penem, were evaluated in comparison with imipenem (IPM), meropenem (MEPM), ceftazidime (CAZ) and flomoxef (FMOX). Sulopenem had broad and potent antibacterial spectra against Gram-positive and Gram-negative bacteria, including Enterococcus faecalis, Proteus vulgaris, Morganella morganii, Enterobacter spp. and Citrobacter freundii. Sulopenem showed concentration-dependent bactericidal activities against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Acinetobacter calcoaceticus. Morphological observation using phase-contrast microscope revealed that sulopenem induced spherical cell formation with E. coli and K. pneumoniae at lower concentrations and bacteriolysis at higher concentrations. Therapeutic efficacies of sulopenem against systemic infections in mice were almost equal to those of imipenem against Streptococcus pneumoniae. While its therapeutic efficacies were superior to those of meropenem, ceftazidime and flomoxef against S. aureus and S. pneumoniae, they were inferior to those of imipenem/cilastatin against S. aureus, K. pneumoniae and A. calcoaceticus.

Animals↗
PubMed1996

Antibiotics, cytokines, and endotoxin: a complex and evolving relationship in gram-negative sepsis.

Compelling experimental evidence now exists that antimicrobial agents induce the release of endotoxin from Gram-negative bacteria during the process of bacteriolysis. Different antimicrobial classes, particularly those which act upon the outer membrane of bacteria, vary in the amount of free endotoxin released from Gram-negative organisms. Despite this in vitro evidence, clinically important consequences of antibiotic-induced endotoxin release have yet to be consistently documented. Complexities in the host-pathogen interactions during actual infection with Gram-negative bacteria may account for the difficulties in demonstrating this phenomena in vivo. This brief review analyses these interactions and defines clinical settings where antibiotic-induced endotoxin release may prove to be clinically relevant.

Anti-Bacterial Agents↗
PubMed1996

Microcalorimetric and electron microscopic investigation on the effects of essential oil from Cymbopogon densiflorus on Staphylococcus aureus.

Microcalorimetry, optical density measurements and electron microscopy, were used to assess the influence of various amounts of the essential oil of Cymbopogon densiflorus (lemongrass oil) on the metabolic activity, growth and morphology of Staphylococcus aureus. Relatively high concentrations of the oil impaired staphylococcal growth in a bacteriostatic manner (chloramphenicol type), and in low doses metabolism became ineffective due to energy losses in the form of heat. Ultrastructural data revealed morphological changes characteristic for the influence of bactericidal antibiotics inducing bacteriolysis (penicillin type). The essential oil may have antibacterial activity by influencing bacterial targets involved in cytoplasmic and cell wall metabolism.

Body Temperature Regulation↗
PubMed1997

[Combination effect between panipenem and vancomycin on highly methicillin-resistant Staphylococcus aureus].

We investigated the in vitro and in vivo combination effects between panipenem (PAPM) and vancomycin (VCM) on highly methicillin-resistant strains of Staphylococcus aureus (MRSA) isolated from various clinical specimens. Examination of combination between panipenem and vancomycin using checkerboard titration showed a good effect with mean fractional inhibitory index of 0.32 +/- 0.12 on 40 MRSA strains, and the effects were judged as synergistic against 33 strains (83%) and additive against 7 strains (17%). In the combination of PAPM and VCM at 1/4 MIC each against exponentially growing MRSA, bactericidal activity was found when PAPM was added at 1 hour or 2 hours prior to VCM-addition, and PAPM with VCM was added simultaneously, although bactericidal activity was scarcely demonstrated when VCM was added at 1 hour or 2 hours prior to PAPM-addition. Bactericidal activity was enhanced against MRSA in the combination of PAPM and VCM at 1/4 MIC each for MRSA than the bactericidal activity of VCM at 1 MIC alone, and the combination showed a strong bactericidal activity against P. aeruginosa. VCM alone, however, had no bactericidal activity in the in vitro mixed cultures of the two bacteria. Furthermore, the combination of PAPM and VCM induced a marked damage to cell surface and bacteriolysis against MRSA and P. aeruginosa in the mixed cultures, although VCM alone induced only slight morphological alterations. Penicillin-binding proteins (PBPs) including MRSA-specific PBP 2' were decreased greatly in the amounts in MRSA-cells with the increase of VCM-treated concentration. The combination therapy of PAPM and VCM showed a greater efficacy than the therapeutic efficacy of each antibiotic alone against mixed infection in burned mice caused by MRSA and P. aeruginosa, and the activity was judged as synergistic based on the FED index smaller than 0.34.

Animals↗
PubMed1979

[Deoxyribonucleic acids from Pasteurella multocida and Pasteurella haemolytica].

Pasteurella multocida and P. haemolytica strains contain between 1.5 and three per cent phosphorus, between nine and 14 per cent nitrogen, between two and four per cent DNA, and between five and 18 per cent RNA, the precise figures depending on culturing conditions. High-molecular DNA may be isolated by means of bacteriolysis, using deoxycholate or dodecylsulphate and the usual steps of purification, with yield and purity differing by strains. DNA with sufficient purity can be obtained from Sepharose 2 B by gel chromatography. The isolated DNA yields were characterised, base values being between 37 and 38 per cent GC for P. haemolytica and between 41 and 48 per cent GC for P. multocida. Highly suitable precursors to DNA synthesis for tritium labelling are 3H-thymidine, which is incorporated in excess of 3H-thymine by a factor of 255, as well as 3H-uracil, with its activity being recovered also from the pyrimidine bases of DNA via pyrimidine biosynthesis.

Chromatography, Gel↗
PubMed1997

A new simple assay for determining aminoglycoside inactivation in intact cells of Pseudomonas aeruginosa.

Intact cells of aminoglycoside (AG) antibiotic-resistant Pseudomonas aeruginosa usually do not inactivate AG, even though they possess the AG-modifying enzyme. An assay method for determining the activity of inactivating enzyme in intact cells of streptomycin-resistant P. aeruginosa was previously reported. Although this assay method was applied to the determination of the activity of kanamycin (KM)-inactivating enzymes, it could not apply to some of the KM-resistant strains. A new simple assay method has now been investigated for determining the activity of KM-inactivating enzyme in intact cells of clinically isolated KM-resistant P. aeruginosa. The determination of AG-inactivating enzyme activity was attempted using lysozyme for release of the inactivating enzymes in washed cells, and both DNase and RNase were added to digestion of the nucleic acids released by bacteriolysis. This lysozyme-DNase-RNase (LDR) method has facilitated the confirmation of the presence of AG-inactivating enzyme in the strains used. In addition, the LDR technique was applicable to the determination of inactivating enzyme activity for various AGs other than KM. Since this simple assay method can determine any type of AG-inactivating enzyme activity of various P. aeruginosa strains, it may contribute significantly to the rapid selection of drugs in clinical use.

Anti-Bacterial Agents↗
PubMedDate not supplied

Further characterization of a complement-sensitive mutant of a virulent avian Escherichia coli isolate.

An attempt was made to characterize the mechanism of complement resistance operating in a virulent avian Escherichia coli isolate. Using flow cytometry to detect antibody to C3, we found that there was significantly more antibody bound to a complement-sensitive mutant of this wild type than to the parent organism, suggesting that more C3 subunits were bound to the wild type. Neither the wild type nor the mutant degraded C3. Further, the mutant was phagocytosed to a significantly greater degree than the wild type by cultured phagocytes in the presence of C5-deficient serum. These data suggest that the wild type is resistant to complement, at least in part, because of its ability to restrict C3 deposition on its surface. Therefore, the decrease in virulence seen in the mutant may be related to its increased sensitivity to complement-mediated bacteriolysis or its enhanced susceptibility to complement-opsonized phagocytosis or both.

Animals↗
PubMed1998

Bactericidal monoclonal antibodies that define unique meningococcal B polysaccharide epitopes that do not cross-react with human polysialic acid.

The poor immunogenicity of the Neisseria meningitidis group B polysaccharide capsule, a homopolymer of alpha(2-->8) sialic acid, has been attributed to immunologic tolerance induced by prenatal exposure to host polysialyated glycoproteins. Substitution of N-propionyl (N-Pr) for N-acetyl groups on the meningococcal B polysaccharide, and conjugation of the resulting polysaccharide to a protein carrier, have been reported to yield a conjugate vaccine that elicits protective Abs with minimal autoantibody activity. To characterize the protective epitopes on the derivatized polysaccharide, we isolated 30 anti-N-Pr meningococcal B polysaccharide mAbs. These Abs were heterogeneous with respect to complement-mediated bactericidal activity, fine antigenic specificity, and autoantibody activity as defined by binding to the neuroblastoma cell line, CHP-134, which expresses long-chain a(2-->8)-linked polysialic acid. Eighteen of the Abs could activate complement-mediated bacteriolysis. Seven of these 18 Abs cross-reacted with N-acetyl meningococcal B polysaccharide by ELISA and had strong autoantibody activity. Thus, N-Pr meningococcal B polysaccharide conjugate vaccine has the potential to elicit autoantibodies. However, 7 of the 18 bactericidal mAbs had no detectable autoantibody activity. These Abs may be useful for the identification of molecular mimetics capable of eliciting protective Abs specific to the bacteria, without the risk of evoking autoimmune disease.

Animals↗