Population Structure of Invasive and Colonizing Strains of Streptococcus agalactiae from Neonates of Six U.S. Academic Centers from 1995 to 1999

Abstract

The purpose of this study was to describe the population structure of group B streptococci (GBS) isolated from infected and colonized neonates during a prospective active-surveillance study of early-onset disease in six centers in the United States from July 1995 to June 1999 and to examine its relationship to bovine strains of GBS. The phylogenetic lineage of each GBS isolate was determined by multilocus sequence typing, and isolates were clustered into clonal complexes (CCs) using the eBURST software program. A total of 899 neonatal GBS isolates were studied, of which 129 were associated with invasive disease. Serotype Ia, Ib, and V isolates were highly clonal, with 92% to 96% of serotype Ia, Ib, and V isolates being confined to single clonal clusters. In contrast, serotype II and III isolates were each comprised of two major clones, with 39% of serotype II and 41% of serotype III isolates in CC 17 and 41% of serotype II and 54% of serotype III isolates in CC 19. Further analysis demonstrates that the CC 17 serotype II and III GBS are closely related to a previously described "ancestral" lineage of bovine GBS. While 120 (93%) of invasive GBS were confined to the same lineages that colonized neonates, 9 (7%) of the invasive GBS isolates were from rare lineages that comprised only 2.7% of colonizing lineages. These results are consistent with those for other geographic regions that demonstrate the highly clonal nature of GBS infecting and colonizing human neonates.Streptococcus agalactiae (group B streptococci [GBS]), a primary cause of bovine mastitis, emerged in the 1960s as a significant human pathogen that causes neonatal sepsis and meningitis (1). Despite a recent decline in incidence, GBS remains a leading cause of neonatal mortality and morbidity in the United States (2,7,29,30). GBS colonizes the genitourinary and gastrointestinal tracts of about a third of healthy adult women (24). Neonatal disease results from transmission of the organism from the pregnant mother to the neonate. Heavy colonization of the neonate and maternal chorioamnionitis are known risk factors for neonatal infection (10,20).GBS can be divided into nine serotypes based on the immunologic reactivity of the capsular polysaccharide. The structure of GBS capsular polysaccharide is determined by genes in the cps locus which encode enzymes responsible for the synthesis of the polysaccharides (8,34,35). Investigators using a variety of techniques have demonstrated that the population of GBS that colonizes and infects humans is comprised of a relatively small number of lineages (4, 12-16, 23, 26, 28, 31, 32). Each serotype is usually distributed among several different lineages, and each lineage may contain several different serotypes, indicating that serotype alone is not a sufficient marker to identify a phylogenetic lineage and suggesting that serotype switching occurs within lineages, presumably by horizontal transfer of cps genes (4,16,23).Multilocus sequence typing (MLST) has become the standard method for determining the population s...

The Threat of Aerobic Vaginitis to Pregnancy and Neonatal Morbidity

“…A prevalence of 7 -25% GBS colonization in AV has been reported in women between 35 and 37 weeks of gestation 54 , with intrauterine infection associated with the ability of GBS to ascend from the lower genital tract and colonize the upper genital tract [54][55][56] . In the newborn, GBS infection may be congenital or acquired 22,57 and remains the foremost cause of neonatal mortality and morbidity in the world despite a recent decline in occurrence 48,52,58,59 . GBS early-onset disease (EOD) occurs at the age of 0-6 days and has been associated with the presence of GBS in the vagina of the mother with transmission thought to take place vertically through aspiration of infected amniotic fluid or passage through the birth canal [60][61][62] , while lateonset disease (LOD), occurs at age between 7 and 90 days 48,62,63 with the source of infection attributed to community or nosocomial acquisition 62 .…”

“…The gastrointestinal tract serves as the natural reservoir for GBS and is expected to be the source of vaginal colonization 23,43 . Pregnant women who are colonized with GBS might develop infections of the urinary tract, bacteremia, chorioamnionitis, and postpartum endometritis 23,47,48 , thus increasing the risk of PTD, PPROM and perinatal transmission [49][50][51] , resulting in neonatal sepsis and meningitis 45,52,53 . A prevalence of 7 -25% GBS colonization in AV has been reported in women between 35 and 37 weeks of gestation 54 , with intrauterine infection associated with the ability of GBS to ascend from the lower genital tract and colonize the upper genital tract [54][55][56] .…”

Differing mechanisms of surviving phagosomal stress among group BStreptococcusstrains of varying genotypes

“…Several studies have shown that serotype III strains belonging to ST-17 are more often associated with neonatal disease, indicating that ST-17 strains may be inherently more virulent than strains of other GBS lineages. [4][5][6][7][8] Additionally, a previous study that examined the GBS colonization status of pregnant women before and after delivery showed that serotype III ST-19 and ST-17 strains were more likely to persistently colonize women after receiving intrapartum antibiotic prophylaxis (IAP), whereas ST-12 strains were more frequently lost. 9 This ability of certain GBS STs to persist suggests an enhanced ability to evade the effect of antibiotics, either through enhanced antibiotic tolerance or protection via biofilm production or uptake into host cells.…”

Sequence type 1 group B Streptococcus , an emerging cause of invasive disease in adults, evolves by small genetic changes

“…Only a few studies of serotype V strains have investigated the noncapsular genetic makeup of the strains, and those that have done so have included colonizing and invasive GBS strains isolated from infants or have not described the clinical origin of the tested strains (18,19). Thus, we sought to analyze a large cohort of clinically well-defined, geographically distinct, and temporally disparate GBS isolates by using a whole-genome approach to elucidate the population structure of serotype V GBS causing invasive disease in nonpregnant adults.…”