lipoteichoic-acid and Infant--Newborn--Diseases

Lipoteichoic acids (LTA) of serotype III strains of group B streptococci (GBS) were shown to mediate adherence of these organisms to human embryonic (HEC), fetal (HFC), and adult buccal (HBEC) epithelial cells. The binding of GBS was temperature dependent, and maximum attachment occurred at 37 degrees C. HEC, HFC, and HBEC preincubated with purified LTA significantly inhibited attachment of GBS, whereas the group B and type III antigens had no effect. Under phosphate-limiting conditions in which cell-associated LTA could not be detected in these organisms, bacterial adherence did not take place. GBS (virulent) that were isolated from infected infants and previously shown to have significantly higher quantities of cell-associated LTA in comparison to GBS strains from asymptomatically colonized infants adhered with greater binding avidity to HEC and HFC and in greater numbers than to HBEC. It was determined that the mechanism of LTA-mediated adherence of GBS to HBEC differed from adherence to embryonic and fetal cells for both virulent and asymptomatic GBS strains bound to HBEC in a similar manner, enhanced by the lipid portion of the LTA. In contrast, the binding of GBS to HEC and HFC was mediated by hydrophobic as well as specific interactions due to the glycerolphosphate polymer of LTA. These results indicate that possible receptor sites for LTA present on cells in prenatal stages of development may differ from those of adult cells, which may result in increased susceptibility of newborn infants to group B streptococcal disease. The implications of LTA-mediated adherence of GBS and their possible role as virulence factors are discussed.

Topics: Adult; Brain; Cell Adhesion; Epithelium; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lipopolysaccharides; Lung; Phosphatidic Acids; Pregnancy; Streptococcal Infections; Streptococcus agalactiae; Teichoic Acids

Cell-associated lipoteichoic acids (LTAs) from late-exponential-phase cultures (serotypes Ia, Ib, Ic, II, and III) of group B streptococci isolated from infected and asymptomatically colonized infants were quantitated and characterized by growing the organisms in a chemically defined medium containing [3H]glycerol and [14C]acetate. Cell pellets were extracted with 45% aqueous phenol and chloroform-methanol and subjected to DEAE-Sephacel anion-exchange chromatography. Elution profiles resolved three major peaks, I, II, and III, with glycerol and phosphate present in a 1:1 molar ratio in each peak, and results obtained by Ouchterlony immunodiffusion analysis confirmed the presence of poly(glycerol phosphate). Saponification indicated that [14C]acetate was incorporated into fatty acids of peaks I and II only, suggesting that these were cell-associated LTAs. Peak II was of small molecular weight (less than 10,000) and probably represented another species of LTA. Peaks I and II were further demonstrated to be LTA by their ability to sensitize human type O erythrocytes. Peak III lacked fatty acids and was shown to probably be deacylated LTA. Quantitation of cell-associated teichoic acid material produced by the group B streptococcal strains indicated that the clinical isolates from infants with early- or late-onset disease possessed significantly higher levels than did the asymptomatic (clinical isolates from infants without symptoms of disease) group B streptococcal strains.

Topics: Cell Wall; Erythrocytes; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lipopolysaccharides; Phosphatidic Acids; Serotyping; Streptococcal Infections; Streptococcus agalactiae; Teichoic Acids

An animal model of maternal-newborn transmission of group B streptococci (GBS) was developed. Pregnant Swiss-Webster mice were colonized by applying 10(8) GBS to the oral cavity, vagina, and nipples daily for 3 days before delivery. Lipoteichoic acid (LTA) from type III GBS or phosphate buffered saline was applied topically to the oral cavity, perineum or nape of newborn mice. Cultures of newborn mice at 3 days of age revealed 35 of 75 (47%) controls and 0 of 79 animals given 2 doses of LTA (2 mg/ml) were positive for GBS at one or more sites. One to two% of control and LTA-treated mice remained culture positive at 7 days of age. None developed GBS disease and no obvious toxicity was noted. This is the first in vivo evidence that colonization with GBS can be prevented by interfering with their adherence to epithelial surfaces. LTA also prevented colonization by 60,000 GBS in the oral cavity of 1-day-old newborn mice. A minimum concentration of 0.5 mg LTA/ml was required and similar dose response curves were obtained in preventing maternal-newborn transmission or oral newborn colonization. LTA from type III GBS also protected against types Ia and II. Only 6 of 15 (40%) vaginally colonized, nonpregnant mice became noncolonized 3 days after LTA treatment. Topically applied lipoteichoic acid from group B streptococci may be a useful method of preventing GBS colonization and/or disease in human infants at birth if it is nontoxic. The method avoids the problems associated with antibiotic prophylaxis and vaccine development.

Topics: Animals; Disease Models, Animal; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lipopolysaccharides; Mice; Phosphatidic Acids; Streptococcal Infections; Streptococcus agalactiae; Teichoic Acids