Prevention of Group B Streptococcal Colonization with Topically Applied Lipoteichoic Acid in a Maternal-Newborn Mouse Model

Abstract

SummaryAn animal model of maternal-newborn transmission of group B streptococci (GBS) was developed. Pregnant Swiss-Webster mice were colonized by applying 10' GBS to the oral cavity, vagina, and nipples daily for 3 days before delivery. Lipoteichoic acid (LTA) from type 111 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 I11 GBS also protected against types Ia and 11. Only 6 of 15 (40%) vaginally colonized, nonpregnant mice became noncolonized 3 days after LTA treatment. SpeculationTopically 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.Group B streptococci (GBS) are a significant cause of neonatal morbidity and mortality. Early onset disease, characterized by sepsis and meningitis, is the more common type and is acquired from the ano-genital tract of the mother at birth (3, 4). Attempts at antibiotic prophylaxis in newborn infants (14, 17) and pregnant women (19) have met with varied success and further study is needed. Development of a vaccine for antibody deficient mothers will be difficult and time-consuming (4). Development of alternate methods of prophylaxis are needed.In 1975, Beachey (6) showed that lipoteichoic acid (LTA) in the cell wall of group A streptococci was responsible for binding of these organisms to oral mucosal cells in vitro. Pretreatment of oral epithelial cells with purified LTA inhibited 78% of added streptococci from binding. In 1977, Ofek et al. (12) showed that LTA from group A streptococci inhibited group B streptococcal binding --to the same degree.Topical application of LTA to a mucosal surface at birth could potentially prevent or reduce colonization with GBS. This method would avoid the disadvantages of antibiotic prophylaxis and some of the difficulties in vaccine development. Because the method has not been tested in vivo, an animal model of maternal-newborn transmission of GBS was developed. MATERIALS AND METHODSOrganisms. Prototype strains type I a (SS-615) and type I1 (SS-619) and wild strain type 111 (DS-2434-80), beta-hemolytic group B streptococci were supplied by Richard Fa...

Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid

“…A recent report showed that free LTA specifically blocks intracellular invasion of Hep2 pharyngeal epithelial cells by S. pyogenes without affecting overall cellular adherence (44). In vivo, topical administration of LTA has also been shown to be effective in blocking vaginal colonization of pregnant mice by GBS (45). Our findings in invasion assays performed in the presence of ∆iagA supernatants containing high levels of released LTA appear to support these earlier observations.…”

Lack of Toxicity of Oral and Intrapulmonary Group B Streptococcal Lipoteichoic Acid

“…In a previous study, topical oral and cutaneous application of LTA to newborn mice was nontoxic and com~letelv re vented GBS colonization of neonates by their vaginall;colok~ed mothers (5). Topical application of LTA to human neonates may also prevent GBS colonization after contact with maternal mucosal and skin surfaces at birth.…”

“…Four hours after intradermal injection, LTA from group A streptococci was found in the cortical tubular regions closely associated with glomeruli, but glomeruli themselves showed little LTA deposition (17). The absence of oral absorption of LTA may be due to its rapid adherence to and slow elution from cell membranes (5,28,29).…”

“…A previous study has shown that LTA from GBS completely inhibits maternal-newborn transmission of GBS in a newborn mouse model (5). No toxicity was observed but specific tests of dose response, absorption, and excretion were not performed.…”

Adherence of group B streptococci to buccal epithelial cells in neonates with different gestational ages

“…Attachment is mediated by lipoteichoic acid (LTA) [4,11,12] on the surface of GBS. Receptor sites for GBS on neonatal cell surfaces may differ from those on adult cells [11] and explain, in part, the increased susceptibility of newborn infants to GBS disease.…”