Genomic characterization of methicillin-susceptible Staphylococcus aureus – An emerging aetiologic agent of concurrent bacteraemia in dengue patient

Abstract

Background: Concurrent bacteraemia in dengue patient is uncommon but most often will result in severe adverse clinical outcome. The major bacterial aetiologic agents of dengue dual infections (DDIs) are members of the Enterobacteriaceae family. During recent years, Staphylococcus aureus (S. aureus) has emerged as an important bacterial pathogen causing DDIs. In cases of staphylococcal co-infection in dengue patients, the methicillin-susceptible phenotype seems to predominate over the resistant phenotype, although the reason behind this phenomenon remains obscured. Therefore, we aim to investigate the genomic features of a methicillin-susceptible S. aureus (MSSA) strain isolated from a dengue patient, in order to elucidate the possible genetic drives for the pathogenicity of this organism. Methods and materials: A methicillin-susceptible S. aureus strain (referred as HS-MSSA) was isolated from the blood culture of a patient initially diagnosed with dengue fever, but later succumbed to septic shock within 24 h post-admission. Antimicrobial susceptibility test showed that the HS-MSSA strain was pan-susceptible to all tested antibiotics. The genomic DNA of the HS-MSSA strain was extracted and subjected to whole genome sequencing and genomic analyses. Results: The draft genome of the HS-MSSA strain is 2.78 Mb in size, harbouring 2643 coding sequences (CDSs). A comparative analysis with the S. aureus reference genome NCTC8325 showed 2415 common genes. A total of 118 CDSs were found unique to the HS-MSSA genome, comprising of mainly phage proteins, mobile genetic elements, and efflux pumps. Majority of the unique CDSs were found in two genomic regions with considerable genetic variation when aligned to the reference genome NCTC8325. One of the genomic regions was found showing greater genetic similarity to methicillin-resistant S. aureus (MRSA) genomes in the NCBI Genbank repository, and harboured multiple phage-associated virulence factors (β-hemolysin, cytolytic pore-forming proteins, etc.). Another genomic region (contig-13) resembled an insertion on which multiple exotoxins and super-antigenic enterotoxins (SEC3 and SElL) were found encoded by two pathogenicity islands, namely SaPI and SaPIn2. Conclusion: We infer that the gaining of multiple virulence determinants during the evolution of the MSSA population might have caused the organism to be more invasive and pathogenic when compared to its antimicrobial-resistant counterpart.