A case of neonatal infection caused by Streptococcus agalactiae sequence type 283 in China’s mainland

Abstract

Figures

Genetic characterization of the S. agalactiae ST283 strain obtained from the blood of a neonate and download data. Phylogenetic tree of the 241 GBS genomes with the reference strains. The S. agalactiae SG-M158, which was sequenced using third-generation sequencing, was used as the reference strain. Blue circles denote virulence genes and red diamonds denote antibiotic resistance genes. Empty shapes represent the absence and filled shapes represent the presence of the respective genes. The right plot is a magnified view of the region within the red square.

Full text

Introduction

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a leading cause of neonatal sepsis, meningitis and pneumonia worldwide. Sequence type 283 (ST283), a hypervirulent lineage of GBS serotype III, has been implicated in large-scale foodborne outbreaks in Southeast Asia, particularly in Singapore, Hong Kong and Thailand.^1,2^ These outbreaks were primarily linked to consumption of or contact with raw freshwater fish, with >380 reported cases to date (Table S1, available as Supplementary data at JAC-AMR Online). While ST283 has been isolated from both humans and animals, its role in neonatal infections has been rarely documented, with only one previous case of early-onset disease (EOD) reported in Hong Kong and a total of four neonatal infections cases reported worldwide.^3,4^ No cases of ST283 infection have been reported in China’s mainland.

Here, we describe the first case of EOD caused by ST283 in China’s mainland, providing evidence for maternal–neonate transmission and highlighting the potential for this clone to colonize mothers and infect neonates.

The study

The index case was a term neonate (38 + 3 weeks gestation, birth weight 3220 g) delivered vaginally to a healthy 26-year-old mother with no history of fever or infectious diseases. The neonate developed respiratory distress and lethargy within 6 hours of birth. Blood culture of the neonate grew S. agalactiae and the isolate was named as ZJSX030. The neonate achieved complete clinical recovery following a 10-day course of intravenous penicillin therapy.

We performed third-generation sequencing (PacBio) on the isolate, followed by de novo assembly using Unicycler (v.0.5.0) to generate its complete genomic map. The sequence data were deposited in the National Genomics Data Center under BioProject ID NMDC10020060. In silico MLST confirmed the isolate as ST283. To compare this isolate with other ST283 isolates, we downloaded all available S. agalactiae ST283 genomic sequences from the PubMLST (https://pubmlst.org/). Detailed information on these 241 isolates was presented in Table S2. A phylogenetic tree for all genomes from the PubMLST database and ZJSX030 was constructed based on their core-genome SNPs using Snippy version 4.4.6 and FastTree. The genome of isolate SG-M158 (GCA_002197265.1) was used as a reference, which represents a fully closed, high-quality genome of the ST283 lineage.^5^

Phylogenetic analysis showed high genetic homogeneity in ST283 isolates across hosts, geographic regions, and previously reported isolates outside China’s mainland. As shown in Figure 1, the ZJSX030 isolate is closely related to two animal-derived ST283 isolates from Thailand. As previously reported, ST283 is a zoonotic Asian GBS clone capable of colonizing and infecting various farmed freshwater fish, causing unusually severe invasive disease in humans. To elucidate the relationship between ZJSX030 and the two subtypes, we analysed the SNPs between them (Figure S1). There is minimal difference between animal-derived and human-derived ST283 strains, with ∼15 SNPs. Interesting, we found guaA, thiM, gtaB, rcsC, glnA, pepO, norm, rsmA and licR harboured missense mutations. Mutations in guaA may enhance the production of nucleotide precursors, which not only accelerates bacterial proliferation within the host but also improves the bacterium’s ability to tolerate nutrient scarcity.^6^  rcsC regulates capsule synthesis and stress responses, thereby enhancing immune escape and increasing the bacterium’s adaptability to the host environment.^7^ The SNPs in these genes may confer an adaptive advantage in human, necessitating further research.

Genetic characterization of the S. agalactiae ST283 strain obtained from the blood of a neonate and download data. Phylogenetic tree of the 241 GBS genomes with the reference strains. The S. agalactiae SG-M158, which was sequenced using third-generation sequencing, was used as the reference strain. Blue circles denote virulence genes and red diamonds denote antibiotic resistance genes. Empty shapes represent the absence and filled shapes represent the presence of the respective genes. The right plot is a magnified view of the region within the red square.

To initially assess the virulence and resistance potential of this strain, we performed a comprehensive analysis of its virulence factors and antimicrobial resistance patterns (Figure 1). ZJSX030 carried the characteristic ST283 virulence gene suite, including: cfb, cylE, pavA, α protein family (Alpha), Srr1, hylB and Lmb. Genome screening identified the tetracycline resistance gene tetM and the macrolide resistance gene mefA in strain ZJSX030. These results were consistent with the antimicrobial susceptibility test findings, which showed resistance to tetracycline (MIC >8 mg/L) and erythromycin (MIC >4 m/L), as well as susceptibility to penicillin, Clindamycin, levofloxacin, vancomycin, linezolid and ceftriaxone.^8^

Discussion

This is the first report of ST283-associated neonatal sepsis in China’s mainland. The isolate’s genomic similarity to fish-derived strains from Thailand supports the hypothesis that ST283 is a zoonotic clone. The mother of the neonate denied any exposure to fish and aquatic products within 1 month before delivery. Although we were unable to obtain vaginal or rectal swabs from the mother due to the retrospective nature of the case, the timing of symptom onset (within 24 hours of birth) strongly supports EOD resulting from vertical transmission.^9^ This case expands the epidemiologic profile of ST283 beyond foodborne illness and highlights its potential as a neonatal pathogen.^4^

Conclusions

S. agalactiae ST283 is no longer restricted to foodborne transmission. Its emergence as a cause of neonatal sepsis in China’s mainland underscores the need for enhanced antenatal surveillance, molecular epidemiology and public health preparedness to prevent further spread of this hypervirulent clone. We recommend investigating gastrointestinal colonization as a potential reservoir for ST283.

Supplementary Material

dlag002_Supplementary_Data