Staphylococcus aureus isolates from children with clinically differentiated osteomyelitis exhibit distinct...

Area of Science:

• Microbiology
• Genomics
• Pediatric Infectious Diseases

Background:

• Genomic heterogeneity exists in Staphylococcus aureus isolates from pediatric acute hematogenous osteomyelitis (AHO).
• Transcriptional behavior of clinically differentiated S. aureus strains in AHO has not been previously described.

Purpose of the Study:

• To evaluate the transcriptional activity of S. aureus isolates from children with AHO.
• To understand how transcriptional regulation influences bacterial growth, metabolism, biosynthesis, and virulence during pathogenesis.
• To compare transcriptional profiles of isolates from mild, moderate, and severe AHO cases.

Main Methods:

• Compared in vitro growth kinetics of three S. aureus clinical isolates from children with varying AHO severity.
• Performed total RNA sequencing at six time points during logarithmic growth for each isolate.
• Utilized NASA RNA-Sequencing Consensus Pipeline for differential gene expression analysis.
• Applied Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.

Main Results:

• S. aureus isolates exhibited differing growth kinetics; the mild isolate showed significantly higher growth rates.
• Distinct transcriptional signatures were identified based on sampling time and clinical severity.
• Moderate and severe isolates were enriched in pathways related to bacterial invasion, S. aureus infection, quorum sensing, and two-component systems.
• The mild isolate showed enrichment in biosynthesis and metabolism pathways.

Conclusions:

• Transcriptional regulation in S. aureus during growth impacts pathogenetic mechanisms and disease severity in childhood osteomyelitis.
• A trade-off between bacterial growth and virulence was observed in the clinical isolates studied.
• Further research in animal models and during active clinical infections is warranted to validate these findings.