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Biomedical subjects

M S Bronze

Publications and source records attributed to M S Bronze.

29 records · Page 2Linked to original sources
PubMed1994

Passive protection of mice against group A streptococcal pharyngeal infection by lipoteichoic acid.

Previous studies have shown that lipoteichoic acid (LTA) of group A streptococci plays a central role in the adherence of these organisms to epithelial cells. In this study, intranasal instillation of purified LTA but not deacylated LTA in mice blocked colonization and prevented death after intranasal challenge infection with group A streptococci. Bacteria pretreated with rabbit antisera against LTA also failed to colonize or infect mice after intranasal challenge. In vitro studies showed that LTA and M protein inhibited adherence of type 24 streptococci to mouse pharyngeal cells. Passive intranasal administration of purified type 24 M protein protected mice from death after challenge infection with type 24 streptococci but had no significant effect on pharyngeal colonization. Surface LTA and M protein may mediate adherence of streptococci to mouse pharyngeal cells, and blocking adherence with LTA prevents colonization and infection in this animal model.

Animals↗
PubMed1994

Analysis of the role of M24 protein in group A streptococcal adhesion and colonization by use of omega-interposon mutagenesis.

We recently concluded that M protein mediates adherence of group A streptococci to HEp-2 tissue culture cells, because the N-terminal half of M protein blocked adherence and M+ strains attached in greater numbers than M- streptococci. To further assess the role of M protein in adhesion, an M-, isogenic mutant of M type M-, isogenic mutant of M type 24 group A streptococci was constructed by insertional inactivation of the emm24 gene with the omega-interposon flanked by emm24 gene sequences. Southern blot analysis confirmed that the omega-element inserted only into emm24. The M- isogenic mutant M24-omega 3 did not react with antiserum to M24 protein, not did it survive in whole human blood. Electron micrographs of M24-omega 3 showed a diminution of surface fibrillae and reduced binding of plasma components compared with the parent strain. The adhesion of the M+ parent to HEp-2 cells and to mouse oral epithelial cells was dramatically greater than the adhesion of the M24-omega 3 mutant, although there was no difference between the two in adhesion to human buccal cells. In addition, the parent strain was dramatically more effective than the M24-omega 3 mutant in colonizing the oral cavity of mice. These results indicate that the M24 protein can serve as an adhesin in streptococcal attachment to human cells in tissue culture and is important in the colonization of mouse mucosal surfaces.

Adhesins, Bacterial↗
PubMed1993

Epitopes of streptococcal M proteins that evoke antibodies that cross-react with human brain.

There is evidence suggesting that Sydenham's chorea, which is a major manifestation of acute rheumatic fever, may be mediated by streptococcal antibodies that cross-react with the brain. Our studies were undertaken to determine whether streptococcal M protein, the major virulence factor of group A streptococci, evoked antibodies that cross-react with human brain. Rabbits were immunized with pepsin-extracted M protein from rheumatogenic type 6 streptococci. Immune sera were screened for the presence of antibodies that cross-reacted with human brain by indirect immunofluorescence tests and immunoblot analyses. Type 6 M protein evoked antibodies that cross-reacted with several brain proteins and antibody binding to these proteins was completely inhibited by type 6 M protein and partially inhibited by types 5 and 19 M proteins, suggesting that these heterologous M proteins contain conserved brain-cross-reactive epitopes. Using synthetic peptides from several serotypes of M proteins, the conserved brain-cross-reactive epitopes were localized to a decapeptide contained within the covalent structure of the B repeat region of type 6 M protein. These peptides also inhibited brain-cross-reactive antibodies in the serum of a patient with active Sydenham's chorea. Our data indicate that streptococcal M proteins contain brain-cross-reactive epitopes that could potentially be involved in the pathogenesis of Sydenham's chorea.

Acute Disease↗
PubMed1992

Epitopes of group A streptococcal M protein that evoke cross-protective local immune responses.

The present studies were undertaken to identify conserved epitopes of group A streptococcal M proteins that evoke cross-protective mucosal immune responses. Two synthetic peptides copying conserved regions of type 5 M protein, designated SM5(235-264)C and SM5(265-291)C, were covalently linked to carrier molecules and their immunogenicity was tested in laboratory animals. Rabbit antisera against both peptides cross-reacted with multiple serotypes of group A streptococci, indicating that the peptides contained broadly cross-reactive, surface exposed M protein epitopes. Serum antipeptide antibodies adsorbed to the surface of heterologous type 24 streptococci passively protected mice against intranasal challenge infections. Mice that were actively immunized intranasally with each synthetic peptide covalently linked to the B subunit of cholera toxin were protected against colonization and death after intranasal challenge infections with type 24 streptococci in the absence of serum opsonic antibodies. These data confirm and extend previous observations that conserved M protein epitopes evoke cross-protective local immunity and may serve as the basis for broadly cross-protective M protein vaccines.

Amino Acid Sequence↗
PubMed1992

Lipoteichoic acid and M protein: dual adhesins of group A streptococci.

The roles of lipoteichoic acid (LTA) and M protein in the adherence of group A streptococci to human cells were investigated. Both M+ and M- streptococci bound to pharyngeal and buccal epithelial cells in similar numbers. Streptococcal attachment was inhibited by LTA, but not by the pepsin-extracted, amino-terminal half of M protein (pep M), suggesting that M protein does not mediate attachment to these cells. However, a purified, recombinant, intact M protein did block attachment of streptococci to buccal cells. Using synthetic peptides, the inhibitory domain was localized to a region of intact M protein that is within or near the bacterial cell wall. Evidence is presented to suggest that on the surface of streptococci this region of the M protein is probably not accessible for interactions with host cell receptors and that M protein does not mediate attachment to buccal or pharyngeal cells. In contrast, approximately 10-times more M+ streptococci bound to Hep-2 cells than did M- streptococci and pep M protein blocked binding of streptococci to Hep-2 cells. The data suggest that at least two streptococcal adhesins, LTA and M protein, are involved in the adherence of streptococci to certain cells and that the relative contributions of these adhesins to the attachment process depends on the type of host cells used to study adherence.

Amino Acid Sequence↗
PubMed1991

Epitopes of group A streptococcal M protein shared with antigens of articular cartilage and synovium.

Rabbit antisera evoked by purified pepsin-extracted group A streptococcal M proteins were screened for the presence of joint cross-reactive antibodies by indirect immunofluorescence using thin sections of mouse knee joints. Pep M1, M5, and M18 antisera contained antibodies that cross-reacted with chondrocytes, cartilage, and synovium. Immunofluorescence inhibition assays showed that some of the joint cross-reactive epitopes were shared among the three heterologous serotypes of M protein. The pep M5 joint cross-reactive epitopes were localized to three different synthetic peptides of the C-terminal region of pep M5. Immunoblot analyses showed that the M5 joint cross-reactive antibodies recognized two proteins of human synovium and cartilage of molecular mass 56 and 58 kDa. The cross-reactive antibodies binding to the 56-kDa protein were inhibited by purified vimentin in immunoblot inhibition experiments. M protein-specific antibodies from patients with acute rheumatic fever were also shown to cross-react with joint tissue in a pattern similar to the rabbit antisera. Rabbit and human M protein-specific antibodies that were bound to articular cartilage activated significant levels of complement when compared to control serum, suggesting that M protein joint cross-reactive antibodies could potentially be involved in the pathogenesis of ARF and arthritis.

Antibodies, Bacterial↗
PubMed1988

Protective immunity evoked by locally administered group A streptococcal vaccines in mice.

The present studies were undertaken to determine the pathogenicity of group A streptococci introduced intranasally (i.n.) into mice in an attempt to mimic mucosal infections in humans and to determine the efficacy of streptococcal vaccines administered via the mucosal route. The LD50 of type 24 streptococci (M24 strep) administered i.n. was 3 x 10(4) CFU. Throat cultures were performed in M24 strep-inoculated mice. Of 11 mice that died, 9 had positive throat cultures 3 or 4 days after i.n. challenge, and of 9 mice that survived, only 1 had a positive throat culture, indicating an association between mucosal infection and death. Postmortem examination performed on 35 mice that died after i.n. challenge showed that all had evidence of disseminated infections, and group A streptococci were recovered from the cervical lymph nodes, blood, spleen, liver, and brain. To determine vaccine efficacy, heat-killed M24 strep or pep M24 were administered i.n. to groups of mice. Whole, heat-killed streptococci and pep M24 administered locally protected mice against death from i.n. challenge infections with homologous M24 strep. The whole cell vaccine also protected against i.n. challenge infections with heterologous type 6 streptococci. Our data suggest that streptococcal vaccines administered locally evoke protective immunity against streptococcal infections.

Administration, Intranasal↗
PubMed1988

Protective and heart-crossreactive epitopes located within the NH2 terminus of type 19 streptococcal M protein.

M protein was purified to homogeneity from limited pepsin digests of intact type 19 streptococci (pep M19). The purified pep M19 when emulsified in CFA and injected into rabbits evoked type-specific and crossreactive opsonic antibodies, as well as heart-crossreactive antibodies. The NH2-terminal primary structure of pep M19 was determined and a peptide copying the first 24 amino acids [SM19(1-24)C] was chemically synthesized. Rabbits that were immunized with the unconjugated peptide developed antibodies that recognized the native pep M19, as determined by ELISA, and opsonic antibodies against type 19 streptococci, as determined by in vitro opsonophagocytosis tests. The synthetic peptide also evoked antibodies that crossreacted with a 60-kD sarcolemmal membrane protein of human myocardium. By using overlapping synthetic subpeptides as immunoinhibitors, the opsonic and heart-crossreactive epitopes of SM19(1-24)C were localized to SM19(11-24)C. Our data confirm the presence of heart-crossreactive epitopes within the primary structure of pep M19 and show that these potentially harmful autoimmune epitopes may be located in the NH2-terminal regions of certain M proteins. We conclude that continued efforts to identify the primary structures of protective and heart-crossreactive epitopes will be necessary to elucidate the pathogenesis of acute rheumatic heart disease and to develop safe and effective streptococcal vaccines.

Amino Acid Sequence↗
PubMedDate not supplied

Intramedullary tuberculomas of the spinal cord: case report and review.

Intramedullary spinal tuberculomas are a rare cause of spinal cord compression. We report a recent case and review 17 cases described in the literature since 1960. Intramedullary spinal tuberculomas occurred in relatively young patients (mean age, 28.6 years) and more frequently in women (63% of cases) than in men. The commonest symptoms were those of subacute spinal cord compression (mean duration, 2.3 months) with progressive lower-limb weakness (94%), paresthesia, and bowel and bladder dysfunction. The major physical finding was paraplegia, either spastic (61%) or flaccid (33%). The majority of patients (55%) had a thoracic sensory level. Extraspinal tuberculous disease, predominantly pulmonary, occurred in 69% of reported cases. Myelography efficiently localized the lesion. The diagnosis was made surgically in 16 patients (89%) and clinically in two (11%). Eleven (65%) of 17 patients improved. Four deaths occurred, three in the perioperative period. Though rare, intramedullary spinal cord tuberculoma should be considered in the differential diagnosis of spinal cord compression, particularly when clinical disease compatible with tuberculosis is present.

Aged↗