Examination of group B streptococcal isolates from infected and asymptomatically colonized infants indicated that isolates from infected infants had three-to-four fold higher levels of lipoteichoic acids (LTA) on their cell surfaces than strains isolated from asymptomatically colonized infants (p less than 0.0001). The concentration of phosphate in the growth medium correlated with the amount of LTA synthesized and retained on the cell surface with levels ranging from non-detectable LTA (grown in 0.5 mM phosphate) to about 100 nmoles LTA/mg cell dry weight (65 mM phosphate). The correlation of LTA levels with infection was apparent at phosphate concentrations above the growth-limiting amount (greater than 1 mM phosphate). Attachment of virulent strains of GBS to human embryonic and fetal cells occurred within five minutes and appeared to be irreversible, in contrast to avirulent and asymptomatic strains, which were easily dissociated from these cells by addition of purified LTA. However, attachment of virulent, avirulent, and asymptomatic serotype III strains could be prevented by pre-incubation of the human embryonic and fetal cells with purified LTA. When virulent serotype III cells were grown under limiting phosphate (0.5 mM), LTA was not synthesized and attachment of the organisms to human embryonic and fetal cells did not occur. In view of these studies and previous data demonstrating the role of LTA in mediating binding of gram positive bacteria to eucaryotic membranes, examination of the role of these polymers in contributing to the virulence of GBS is clearly warranted. The present study proposes to: (1) examine a large number of GBS isolates from infected and asymptomatically colonized infants including representatives of all five serotypes for levels of LTA; (2) determine the chemical composition of LTA from selected isolates obtained from infected and asymptomatically colonized infants; (3) examine the biochemical and biological characteristics of membrane binding of purified lTA and GBS cells determined to have non-detectable and high levels of these polymers, focusing in particular on studies of specificity, affinity and number of LTA binding sites on human embryonic fetal, and adult buccal epithelial cells; (4) determine the ability of LTA to block attachment of GBS to the above cell lines; (5) examine the effect of monospecific and/or monoclonal antibody to purified LTA on attachment of GBS to neonatal cell lines and in passive protection studies in a neonatal rat model.
| Mattingly, S J; Johnston, B P (1987) Comparative analysis of the localization of lipoteichoic acid in Streptococcus agalactiae and Streptococcus pyogenes. Infect Immun 55:2383-6 |
| Nealon, T J; Mattingly, S J (1985) Kinetic and chemical analyses of the biologic significance of lipoteichoic acids in mediating adherence of serotype III group B streptococci. Infect Immun 50:107-15 |
