Multistate, Population-Based Distributions of Candidate Vaccine Targets, Clonal Complexes, and Resistance Features of Invasive Group B Streptococci Within the United States, 2015–2017

Abstract

Background Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development. Methods Using whole genome sequencing, a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6340 invasive GBS isolates recovered during 2015–2017 through population-based Active Bacterial Core surveillance (ABCs) in 8 states. Results Six serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in 11 clonal complexes (CCs) comprised of multilocus sequence types identical or closely related to sequence types 1, 8, 12, 17, 19, 22, 23, 28, 88, 452, and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with nonsusceptibility to 1 or more β-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin nonsusceptible (minimum inhibitory concentration = 2 µg/mL). Nearly all isolates possessed capsule genes, 1–2 of the 3 main pilus gene clusters, and 1 of 4 homologous alpha/Rib family determinants. Presence of the hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed. Conclusions This first comprehensive, population-based quantitation of strain features in the United States suggests that current vaccine candidates should have good coverage. The β-lactams remain appropriate for first-line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring.

Features of Streptococcus agalactiae strains recovered from pregnant women and newborns attending different hospitals in Ethiopia

“…The hvgA gene has been detected in previous studies, primarily among highly virulent S. agalactiae belonging to serotype III/ST17 [27] and rarely found among nonserotype III isolates [14,28]. Two hvgA positive isolates in our sampling were of serotype Ia/ST934, which is S. agalactiae have generally been considered universally susceptible to penicillin although there have been several reports of isolates with mutations associated with decreased susceptibility over the last decade [12,29,30]. Here, PBP 2X types were restricted to types, 1, 4 and 5, commonly seen in penicillin-susceptible US isolates [5] and all isolates were sensitive to penicillin and cefotaxime.…”

“…A multiplex PCR assay was initially used for the direct identification of the capsular serotypes (Ia to IX) of GBS [17]. In addition, serotype was confirmed using the CDC short-read WGS bioinformatics pipeline [5,12]. The presence of hypervirulent GBS adhesion determinant (hvgA), serine-rich repeat gene (srr), one of four alphafamily surface protein genes (rib, alpha, alp1, alp2/3) and the pilus islands (PI-1, PI-2a, and PI-2b) were also queried through the CDC pipeline (https://github.com/Ben-JamesMetcalf) [12].…”

“…GBS serotype distribution is not uniform across different geographic regions and temporal variations have also been described [9]. As information on GBS from their genomes has accumulated, molecular methods have also proved very useful for investigating the population structure of GBS and discriminating differences between strains isolated from different sources [5,[10][11][12]. For example, the ST17 lineage has been associated with neonatal infections, particularly with late-onset disease [11].…”

“…For example, the ST17 lineage has been associated with neonatal infections, particularly with late-onset disease [11]. There are previous reports showing diversification and shifts in serotypes [5,12,13] and abundant evidence of past capsular switching within several MLST-based lineages [12,14] which also pose potential challenges for the development of a vaccine. Global data on circulating GBS strains is important for disease control and for informing the development of effective vaccines.…”

Invasive group B Streptococcus among non-pregnant adults in Brussels-Capital Region, 2005–2019

“…Regarding antibiotic susceptibility, GBS remains susceptible to penicillin, the first-line treatment. However, reports of reduced susceptibility to penicillin, associated with mutations in penicillin binding proteins, have been published [1,7,12,13]. Since two decades, increased emergence of resistance to clindamycin and erythromycin is reported worldwide [14] and in Belgium [15].…”