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Biomedical subjects

I Ofek

Publications and source records attributed to I Ofek.

137 records · Page 8Linked to original sources

Application of enzyme production properties in subtyping of group A streptococci according to T type.

The production of extracellular nicotinamide adenine dinucleotide glycohydrolase (NADG) and the cell-bound lipoproteinase (serum opacity reaction, SOR) by strains of different serological types of group A streptococci, in relation to the T typing, was studied. The production of both NADG and SOR, or only one of them, was found to be characteristic of serotypes, as determined by M and T antigen. No difference in the production of these enzymes was found in relation to M-positive and M-negative variants. Investigation into NADG and SOR production as related to the T type enabled the division of a single agglutination pattern into four main groups, each of which corresponds to one specific M type or more. Of the 370 strains belonging to 12 different T-agglutination patterns, 21% produced both enzymes and 42.5% failed to produce any of them, whereas the remaining 36.5% produced only one out of the two enzymes. Five streptococcal types which did not produce NADG and SOR also failed to synthesize streptolysin S at the early logarithmic phase of growth, indicating that streptolysin S production by young cultures may be also related to serotype. No correlation was found between the production of NADG-SOR as related to serotype and the production of streptolysin O, acid phosphotase, esterase, N-acetylglucosaminidase, hyaluronidase, streptokinase, and the cell-sensitizing factor. The practical and potential usefulness of NADG and SOR production in epidemiological studies is discussed.

Agglutination Tests↗

Effect of pH on in vitro phagocytosis of Streptococcus pyogenes.

Phagocytosis experiments were performed with mouse peritoneal leucocytes (MPL). The natural pH of the mouse peritoneal cavity was found to be between 6.1 and 6.3. The phagocytic and intracellular killing activities of MPL by pH variations was studied. It was observed that the optimal ingestion and intracellular killing of bacteria is at the natural pH of the peritoneal cavity.

Animals↗

Interaction of bacterial pili and leukocytes.

Since Duguid and Guilles first described the ability of piliated bacteria to bind to leukocytes, much has been learned about the nature of this interaction. Mannose-sensitive (MS) pili bind to specific mannose-containing receptors on the leukocyte surface. While MS pili are responsible for attachment, the relative hydrophobicity of the bacterial surface determines whether the organism is internalized. Both binding and ingestion trigger the leukocyte to respond with degranulation and enhanced oxidative activity. The response to piliated bacteria, however, is delayed as compared to bacteria opsonized with serum, which may account for the reduced bactericidal activity associated with pili-mediated phagocytosis. A number of factors appear to influence the significance of pili-mediated phagocytosis in vivo. These include natural selective pressures in the host tissue, the ability of the organism to undergo pili phase transition and the presence of serum or other host opsonic factors. Antipili antibody does not enhance leukocyte killing of MS + Escherichia coli, but does stimulate leukocyte metabolic activity. Antipili antibody may, therefore, have an adverse effect on the infectious process by promoting the extracellular release of inflammatory material from the granulocyte.

Animals↗

Safe as mother's milk: carbohydrates as future anti-adhesion drugs for bacterial diseases.

The majority of infectious diseases are initiated by adhesion of pathogenic organisms to the tissues of the host. In many cases, this adhesion is mediated by lectins present on the surface of the infectious organism that bind to complementary carbohydrates on the surface of the host tissues. Lectin-deficient mutants often lack ability to initiate infection. Soluble carbohydrates recognized by the bacterial lectins block the adhesion of the bacteria to animal cells in vitro. Moreover, they have also been shown to protect against experimental infection by lectin-carrying bacteria in different organs of mammals such as mice, rabbits, calves and monkeys. In a phase II clinical trial, a pentasaccharide shown to have anti-adhesive activity against Streptococcus pneumoniae and Hemophilus influenzae in vitro failed to protect young children from nasopharyngeal colonization with these organisms and from developing otitis media. This could be because insufficient drug was delivered via nasal spray, because bacteria express multiple specificities, the inhibition of which may require a cocktail of oligosaccharides, or because children have different carbohydrate receptors from those of adults. The results of a clinical trial in which N-acetylneuraminyl(alpha2-3)lactose was administered orally to Helicobacter pylori positive patients in an effort to reduce or eradicate bacterial colonization, are awaited with interest. Although the high cost of production of the required oligosaccharides is falling with the recent introduction of enzymatic methods of synthesis, new technologies, in particular the use of engineered bacteria, promise to lower it even further. Attachment of the oligosaccharides to soluble polymeric carriers will increase greatly their effectiveness as antiadhesion agents. There is no doubt that anti-adhesive oligosaccharides will in the near future join the arsenal of drugs for the therapy of bacterial diseases.

Adult↗

Suppression of bacterial adherence by subminimal inhibitory concentrations of beta-lactam and aminoglycoside antibiotics.

Nonseptate filaments of Escherichia coli obtained by growth of a temperature-sensitive mutant of the organism at its restrictive temperature in the absence of antibiotics or at its permissive temperature in the presence of approximately one-half the MIC of penicillin (27 micrograms/ml; MIC of penicillin, 50 micrograms/ml) lacked the ability both to bind to mannose and to adhere to host tissues. Addition of low concentrations (0.5-10 micrograms/ml) of streptomycin to cultures of E. coli resulted in marked suppression of the mannose-binding and adhering ability of streptomycin-sensitive E. coli (MIC, 30 micrograms/ml). In contrast, up to 5,000 microgram of streptomycin/ml had no effect on an isogenic streptomycin-resistant mutant of E. coli (MIC, 20,000 micrograms/ml). No concentration of penicillin or streptomycin that was tested was able to suppress either the mannose-binding or the adhering ability of E. coli once those activities had been acquired by the organism. These results suggest that subminimal inhibitory concentrations of antibiotics suppress the ability of bacteria to adhere to cells.

Adhesiveness↗

Attachment of Streptococcus pyogenes to mammalian cells.

Accumulated evidence indicates that lipoteichoic acid (LTA) is centrally involved in the attachment of group A streptococci to epithelial cells of the host. The binding of LTA to a variety of host cells is mediated by the glycolipid end of the LTA molecule, which can form ionic complexes with streptococcal surface proteins, permitting the reorientation of the LTA to expose some of its lipid ends toward the surface of the organism. The ability of albumin to block the adherence of streptococci to epithelial cells and to bind to LTA-M protein but not deacylated LTA-M protein complexes supports the idea that the lipid ends remain free to interact with cell membrane receptors. The cell membrane receptors appear to consist of a lipid-binding region(s) on fibronectin molecules on the surfaces of oropharyngeal epithelial cells. Although streptococci exhibit LTA-sensitive binding to phagocytic cells in a serum-free system, in the presence of serum, they do not; rather, complement bound to the streptococcal cell surface is required for recognition by phagocytes. The binding of fibrinogen to the M protein on the surface of M-rich streptococci specifically blocks the recognition of the organisms by opsonic complement components. The attachment of M-rich streptococci to phagocytic cells requires the development of antibodies directed specifically toward regions of M protein not blocked by fibrinogen.

Adhesiveness↗

Interactions of fibronectin with streptococci: the role of fibronectin as a receptor for Streptococcus pyogenes.

Current evidence suggests that lipoteichoic acid (LTA) on the surface of Streptococcus pyogenes is centrally involved in the adherence of these bacteria to the oral mucosa. The major receptor on the surface of buccal mucosal cells for S. pyogenes is fibronectin. Fibronectin is a complex glycoprotein found in blood, extracellular matrices, and saliva. Many species of streptococci bind to fibronectin, although the characteristics of these interactions are different. Furthermore, whereas LTA is an efficient inhibitor of the binding of fibronectin to group A streptococci, it has little ability to inhibit the binding of fibronectin to Streptococcus pneumoniae or Staphylococcus aureus. Studies conducted with fibronectin show that different bacteria bind to different sites. The ability of various bacteria to interact with different domains on the fibronectin molecule may play an important role in bacterial adherence and tissue tropism.

Animals↗