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Updated: Sep 28, 2025

Heuristic Mining of Hierarchical Genotypes and Accessory Genome Loci in Bacterial Populations
Published on: December 7, 2021
Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia
Anita J Campbell1, Shakeel Mowlaboccus2, Geoffrey W Coombs3
1Department of Infectious Diseases, Perth Children's Hospital, Perth, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute. Perth, Australia; School of Medicine, University of Western Australia, Perth, Australia.
Insights
Antimicrobial resistance in Staphylococcus aureus (S. aureus) is critical in childhood infections. Panton-Valentine leukocidin (PVL) positivity in S. aureus bacteraemia (SAB) was the sole molecular predictor of poor outcomes in children.
Area of Science:
- Microbiology and Infectious Diseases
- Genomics and Molecular Epidemiology
- Pediatric Infectious Diseases
Background:
- Staphylococcus aureus antimicrobial resistance (S. aureus) and its toxins are increasingly recognized as significant factors in childhood disease.
- Understanding the genetic basis of S. aureus virulence is crucial for effective clinical management and improving patient outcomes.
- The role of methicillin-susceptible S. aureus (MSSA) in healthcare-associated infections requires further investigation.
Purpose of the Study:
- To explore the role of S. aureus antimicrobial resistance genes and toxins in childhood disease severity and outcomes.
- To analyze whole genome sequencing (WGS) data alongside clinical information for children hospitalized with S. aureus bacteraemia (SAB).
- To identify molecular predictors of poor outcomes in pediatric SAB.
Main Methods:
- A prospective, multisite study involving Australian and New Zealand children hospitalized with SAB between 2017-2018.
- Whole genome sequencing (WGS) was performed on 353 SAB isolates, paired with clinical data from the ISAIAH cohort.
- Analysis included identification of sequence types (STs), clonal complexes (CCs), and the presence of Panton-Valentine leukocidin (PVL).
Main Results:
- Of 353 SAB isolates, 85% were methicillin-susceptible S. aureus (MSSA) and 15% were methicillin-resistant S. aureus (MRSA).
- MSSA was predominant in healthcare-associated SAB (87%), while PVL-positive SAB occurred in 22% of cases, predominantly MSSA and community-onset.
- PVL positivity was the only independent microbiological predictor of poor outcomes in community-onset SAB (aOR 2.6).
Conclusions:
- MSSA plays a significant, previously under-recognized role in harboring genetic virulence and causing healthcare-associated infections in children.
- PVL positivity emerged as the sole molecular independent predictor of poor outcomes in pediatric SAB.
- Further research is needed to understand the implications of PVL-producing S. aureus strains on clinical management strategies.
Objectives:
The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration.
Methods:
A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort.
Results:
353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2]).
Conclusion:
From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management.
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