Group B Streptococcus cpsE Is Required for Serotype V Capsule Production and Aids in Biofilm Formation and Ascending Infection of the Reproductive Tract during Pregnancy

Abstract

Group B Streptococcus (GBS) is an encapsulated Gram-positive pathogen that causes ascending infections of the reproductive tract during pregnancy. The capsule of this organism is a critical virulence factor that has been implicated in a variety of cellular processes to promote pathogenesis. Primarily comprised of carbohydrates, the GBS capsule and its synthesis is driven by the capsule polysaccharide synthesis (cps) operon. The cpsE gene within this operon encodes a putative glycosyltransferase that is responsible for the transfer of a Glc-1-P from UDP-Glc to an undecaprenyl lipid molecule. We hypothesized that the cpsE gene product is important for GBS virulence and ascending infection during pregnancy. Our work demonstrates that a GBS cpsE mutant secretes fewer carbohydrates, has a reduced capsule, and forms less biofilm than the wild-type parental strain. We show that, compared to the parental strain, the ΔcpsE deletion mutant is more readily taken up by human placental macrophages and has a significantly attenuated ability to invade and proliferate in the mouse reproductive tract. Taken together, these results demonstrate that the cpsE gene product is an important virulence factor that aids in GBS colonization and invasion of the gravid reproductive tract.

Analysis of Susceptibility to the Antimicrobial and Anti-Biofilm Activity of Human Milk Lactoferrin in Clinical Strains of Streptococcus agalactiae With Diverse Capsular and Sequence Types

“…However, we did observe differences in GBS biofilm formation. Our group previously described the role of capsule in biofilm formation in GBS (Noble et al, 2021), further bolstering our findings. It is plausible that iron starvation alters capsule-mediated biofilm formation in certain capsular types of GBS.…”

“…The streptococcal polysaccharide capsule facilitates evasion of the innate immune response by protecting the bacterial cell from deposition of complement, opsonization, and phagocytosis (Winkelstein et al, 1980;Brown et al, 1983;Abeyta et al, 2003). A recent study from our laboratory revealed that the GBS capsule aids in biofilm formation and ascending infection of the reproductive tract during pregnancy (Noble et al, 2021). Moreover, the capsule across all serotypes shares terminal sialic acid (Sia) residues that allow molecular mimicry of human cell surface sialic acids.…”

Sequential One‐Pot Three‐Enzyme Synthesis of the Tetrasaccharide Repeating Unit of Group B Streptococcus Serotype VIII Capsular Polysaccharide

“…[ 1‐3 ] The capsular polysaccharides (CPSs) on GBS cell surfaces have been recognized as important virulence factors that contribute to the invasiveness of GBS through enhancement of biofilm formation, interference of complement‐mediated killing, affection of the bacterial adherence, etc . [ 4‐6 ] Owing to their unique and highly conservative structures, CPSs have been widely utilized for the classification of bacterial serotypes and also successfully served as valuable immunotargets for the development of prophylactic bacterial vaccines. [ 7‐8 ]…”

Streptococcus agalactiae npxis required for survival in human placental macrophages and full virulence in a model of ascending vaginal infection during pregnancy

“…GBS infection of pregnant mice and subsequent analyses were performed as previously described (15, 44). Briefly, C57BL6/J mice were purchased from Jackson Laboratories and mated in harem breeding strategies (1 male to 3-4 females) overnight.…”

“…To determine bacterial burden in reproductive tissues, quantitative culture methods were employed as previously described (44). Briefly, reproductive tissues were weighed and placed in sterile THB.…”