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Published on: November 16, 2016
Emerging Fatal Ib/CC12 Hypervirulent Multiresistant Streptococcus agalactiae in Young Infants With Bloodstream
Jingxian Liu1, Feng Chen1, Hongyan Guan1
1Department of Clinical Laboratory, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Insights
A hypervirulent, multidrug-resistant Streptococcus agalactiae (GBS) clone, Ib/CC12, is emerging in pediatric bloodstream infections. This clone exhibits increased virulence and mortality, necessitating focused prevention and control strategies.
Area of Science:
- Microbiology
- Infectious Diseases
- Genomics
Background:
- Group B Streptococcus (GBS) poses a significant threat to young infants.
- Pediatric GBS infections, particularly bloodstream infections (BSI), require ongoing surveillance and characterization.
Purpose of the Study:
- To investigate the characteristics of GBS strains causing pediatric infections in Shanghai.
- To identify specific GBS clones associated with increased virulence, BSI, and mortality.
- To analyze the genetic and virulence factors contributing to GBS pathogenesis.
Main Methods:
- Retrospective analysis of 80 pediatric GBS infection cases (2009-2020).
- Sequence typing (STs) and serotyping of GBS isolates.
- Polymerase chain reaction (PCR) for virulence gene detection.
- In vitro invasion assays using cell lines.
- In vivo murine model for pathogenicity assessment.
- Whole-genome sequencing and comparative genomic analysis.
Main Results:
- The Ib/clonal complex (CC)12 GBS clone was significantly associated with BSIs (86.7%) and higher mortality rates (30.8%) compared to other clones.
- Ib/CC12 strains showed distinct virulence gene profiles, enhanced invasiveness in certain cell types, and rapid systemic invasion in vivo.
- Genomic analysis revealed Ib/CC12 strains possess unique genes, including a toxin/antitoxin system, and carry multiple antibiotic resistance genes (macrolides, clindamycin, aminoglycosides, tetracycline).
Conclusions:
- The Ib/CC12 clone represents an emerging, hypervirulent, and multidrug-resistant GBS strain causing severe pediatric infections.
- Enhanced surveillance and targeted control measures for Ib/CC12 GBS infections are crucial for pediatric patient safety.
Abstract:
Streptococcus agalactiae [also known as group B Streptococcus (GBS)] is a tremendous threat to young infants. Eighty pediatric GBS infection cases were enrolled from a teaching hospital in Shanghai between 2009 and 2020; among them, 72.5% (58/80) were diagnosed with bloodstream infection (BSI). Sequence types (STs) and serotypes of associated GBS strains were identified, and most of the Ib/clonal complex (CC)12 (86.7%, 13/15) strains caused BSIs, which was significantly higher than that of the genetically related clone Ib/CC10 (20%, 2/10; p < 0.05). Ib/CC12 BSI (30.8%) mortality was significantly higher than that of non-Ib/CC12 BSI (2.2%; p < 0.05). Virulence genes associated with adhesion, invasion, and immune evasion were detected using polymerase chain reaction. The fbsA and gbsPC1 positive rates of Ib/CC12 strains was higher than that of non-Ib/CC12 strains, whereas cpsIaJ, cpsJ, cpsI, and cpsG positive rates were lower than those of non-Ib/CC12 (p < 0.05). In in vitro studies, the Ib/CC12 strains had strong invasiveness in RAW264.7 cells, but less invasiveness in human umbilical vein endothelial cells, human brain microvascular endothelial cells, and human mammary epithelial cells when compared to other two clones. In the in vivo model, the Ib/CC12 GBS invaded the circulation system more rapidly after intraperitoneal injection, was more difficult to eradicate by phagocytes, and caused significantly higher mortality than Ib/CC10 and III/ST17 (p < 0.05). Genome analysis showed that the Ib/CC12 strains had two clustered regularly interspaced short palindromic repeat-Cas systems and carried more antibiotic resistant genes, which conferred resistance to macrolides, clindamycin, aminoglycosides, and tetracycline. The Ib/CC12 strains had 45 unique annotated genes compared to that of Ib/CC10, including the pathogen-related toxin/antitoxin system, PezA/T. In conclusion, Ib/CC12 is an emerging hypervirulent multiresistant GBS clone that causes invasive and fatal infections in pediatric patients. The prevention and control of Ib/CC12 GBS infection should be emphasized.
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