Investigation of genetic associations of mother to neonate group B streptococcus
File(s)
Author(s)
To, Ka-Ning
Type
Thesis
Abstract
Group B Streptococcus (GBS, Streptococcus agalactiae) is a leading cause of neonatal infections and stillbirths in infants under 3 months old. Vertical transmission remains the most common route of transmission to infants ≤6 days old due to ingestion of GBS laden fluids during delivery, or in utero. The route of transmission to infants 7-90 days old is less well understood. To understand the genetic distribution of GBS strains from The Gambia, and the associations of mother to infant transmission, we used whole genome sequencing. Genomic analysis of 781 GBS isolates from 154 GBS colonised women and their infants ≤90 days old from The Gambia revealed the most common serotypes were serotypes V (42%), II (27%), III (13%), IV (9%), Ia (7%) and Ib (2%). Multilocus sequence typing (MLST) grouped the isolates into 20 STs, with four novel STs identified which were ST1354, ST1355, ST1356 and ST1357. All GBS isolates clustered into CC1 (43.9%), CC26 (25.9%), CC17 (10%), CC19 (7.2%), CC23 (7.2%) and CC10 (5.1%). Antibiotic resistance was low in GBS in The Gambia. No isolates were resistant to penicillin or clindamycin, but resistance to macrolides (5%), tetracycline (99%), and fluoroquinolones (2.3%) were observed. Using comparative genomics to identify genetic mutations that are associated with mother to infant GBS transmission, multiple mutations were identified in 94 mother-infant pairs colonised with the same ST. Mutations were found in key virulence factors such as bibA and bca, but no gene had a mutation in more than one mother-infant pair, except for mutations in ispE, bioB, rsmB, infB and nylA_1, where each of these genes were found in two mother-infant pairs. Overall, this work shows GBS strains in colonisation are heterogeneous and GBS can undergo genetic changes within a short duration of ≤89 days.
Version
Open Access
Date Issued
2022-01
Date Awarded
2022-05
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Le Doare, Kirsty
Jauneikaite, Elita
Bush, Andrew
Publisher Department
Department of Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)