Genomic characterisation of perinatal Western Australian Streptococcus agalactiae isolates

Abstract

As a leading cause of neonatal sepsis, Streptococcus agalactiae, commonly known as Group B Streptococcus, is a major neonatal pathogen. Current global screening practices employ risk- or culture-based protocols for detection of these organisms. In Western Australia (WA), universal culture-based screening is provided, with subsequent intrapartum antibiotic prophylaxis for all S. agalactiae-positive women during labour. Widespread antibiotic exposure is not ideal and this is one of the factors driving development of vaccines against S. agalactiae. Vaccine candidates have focused on the capsule, surface proteins and pilus types, however, capsule serotypes are known to vary geographically. The aim of this study was to use genome sequencing to gain an understanding of the circulating genotypes in WA, and to assess variations in the associated gene pools. We sequenced 141 antenatal carriage (vaginal/rectal) isolates and 10 neonatal invasive disease isolates from WA. Based on the global PubMLST database, the 151 strains were characterised into 30 sequence types, with clustering of these mainly into clonal complexes 1, 12, 17, 19 and 23. Of the genes encoding eleven surface proteins that were analysed, the most prevalent were fbp, lmb and scpB which were present in ≥ 98% of isolates. A cluster of non-haemolytic isolates, one of which was a neonatal invasive disease isolate, appeared to lack the entire cyl locus. Admixture analysis of population structure revealed evidence of genetic transfer among the WA isolates across structural groups. When compared against the PubMLST S. agalactiae data, WA isolates showed high levels of strain diversity with minimal apparent clustering. This is the first whole genome sequence study of WA S. agalactiae isolates and also represents the first addition of Australian isolate data to PubMLST. This report provides insight into the distribution and diversity of vaccine targets of S. agalactiae within Western Australia, indicating that the most appropriate capsular vaccine for this population would be the proposed pentavalent (Cps Ia, Ib, II, III and V) preparation, whilst vaccines targeting surface proteins should ideally utilise Fbp, Lmb and/or ScpB.

Fig 1

(A) The core genome maximum likelihood phylogeny of 151 clinical Streptococcus agalactiae isolates collected from Western Australian pregnant women (n = 141) and neonates (n = 10). Clonal complexes are highlighted within the tree. The first colour strip indicates antenatal carriage (blue) and neonatal invasive disease (red) isolate origins. The central colour strip indicates carriage site for the antenatal isolates, either vaginal (green) or rectal (orange) and the outer colour strip indicates the capsular genotype (Ia–IX). (B) Admixture analysis of population structure of the same S. agalactiae isolates as defined by BAPS. Isolates are displayed as vertical coloured bars, with colours indicative of the proportion of admixture that has occurred between the isolate and other structural groups.

Fig 2. Maximum likelihood phylogeny tree comparing a global dataset representative of the diversity available in PubMLST to Western Australian isolates.

The clade colouring is indicative of the continent of isolate origin and the outer colour strip indicates the clinical presentation of invasive disease or carriage.