Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates

Abstract

Group B streptococci (GBS) are bacteria that can cause preterm birth and invasive neonatal disease. Heterogeneous expression of virulence factors enables GBS to exist as both commensal bacteria and to become highly invasive. A molecular epidemiological study comparing GBS bacterial traits, genotype and host characteristics may indicate whether it is possible to predict the risk of perinatal invasive GBS disease and more accurately target intrapartum antibiotic prophylaxis. A total of 229 invasive GBS isolates from Swedish pregnant women or neonates were assessed for virulence and phenotypic traits: hemolysis zone, hemolytic pigment (Granada agar), Streptococcus B Carrot Broth (SBCB) assay, CAMP factor, and hyaluronidase activity. Genes regulating hemolytic pigment synthesis (covR/covS, abx1, stk1, stp1) were sequenced. Of the virulence factors and phenotypes assessed, a Granada pigment or SBCB score ≥ 2 captured more than 90% of EOD isolates with excellent inter-rater reliability. High enzyme activity of hyaluronidase was observed in 16% (36/229) of the invasive GBS isolates and notably, in one case of stillbirth. Hyaluronidase activity was also significantly higher in GBS isolates obtained from pregnant/postpartum individuals versus the stillbirth or neonatal invasive isolates (p < 0.001). Sequencing analysis found that abx1 (g.T106I), stk1 (g.T211N), stp1 (g.K469R) and covS (g.V343M) variants were present significantly more often in the higher (Granada pigment score ≥ 2) versus lower pigmented isolates (p < 0.001, each variant). Among the 203 higher Granada pigment scoring isolates, 22 (10.8%) isolates had 3 of the four sequence variants and 10 (4.9%) had 2 of the four sequence variants. Although heterogeneity in GBS virulence factor expression was observed, the vast majority were more highly pigmented and contained several common sequence variants in genes regulating pigment synthesis. High activity of hyaluronidase may increase risk for stillbirth and invasive disease in pregnant or postpartum individuals. Our findings suggest that testing for GBS pigmentation and hyaluronidase may, albeit imperfectly, identify pregnant people at risk for invasive disease and represent a step towards a personalized medical approach for the administration of intrapartum antibiotic prophylaxis.

Molecular characteristics and virulence factors of group B Streptococcus in South Korea according to the invasiveness

“…The serotype III/ST17 strain was the most prevalent in iGBS, whereas the serotype VIII/ST2 strain was the most common in nGBS. These results are similar to the distribution of iGBS serotypes reported in other countries [13,19]. Furthermore, in our study, serotype III was the dominant, followed by serotypes Ia, Ib, II, and V Pili are cell-wall-anchored appendages on GBS cell surface; they play an important role in bacterial attachment to epithelial cells.…”

“…Maternal GBS colonization is a major determinant of EOGBS infections in neonates. European studies have shown similarity in serotype distribution between maternal colonized GBS and iGBS, and this nding indicates that EOGBS infection is caused by GBS transmission from mother to newborn [13,14].…”

Spatial profiling of the placental chorioamniotic membranes reveals upregulation of immune checkpoint proteins during Group B Streptococcus infection in a nonhuman primate model

“…We have established a nonhuman primate model in which GBS are inoculated into the choriodecidual space of the lower uterine segment where ascending bacteria are first thought to contact the placenta ( Adams Waldorf et al., 2011a ; Vanderhoeven et al., 2014 ; McAdams et al., 2015 ; Boldenow et al., 2016 ; Coleman et al., 2020 ; Weed et al., 2020 ; Coleman et al., 2021 ). The virulence of the GBS strain is paramount for the outcome of a choriodecidual infection in that strains of higher virulence have a greater likelihood of ascension into the uterus, placental invasion and preterm birth or stillbirth ( Whidbey et al., 2013 ; Boldenow et al., 2016 ; Vornhagen et al., 2016 ; Armistead et al., 2019 ; Brokaw et al., 2021 ; Coleman et al., 2021 ; Furuta et al., 2022 ; Huebner et al., 2022 ). A key GBS virulence factor is the ornithine rhamnolipid pigment (β-hemolysin), which imparts hemolytic activity, which is produced by gene products in the cyl operon ( Spellerberg et al., 1999 ; Pritzlaff et al., 2001 ; Whidbey et al., 2013 ).…”