Genomic Heterogeneity of Methicillin Resistant Staphylococcus aureus Associated with Variation in Severity of Illness among Children with Acute Hematogenous Osteomyelitis

Abstract

IntroductionThe association between severity of illness of children with osteomyelitis caused by Methicillin-resistant Staphylococcus aureus (MRSA) and genomic variation of the causative organism has not been previously investigated. The purpose of this study is to assess genomic heterogeneity among MRSA isolates from children with osteomyelitis who have diverse severity of illness.Materials and MethodsChildren with osteomyelitis were prospectively studied between 2010 and 2011. Severity of illness of the affected children was determined from clinical and laboratory parameters. MRSA isolates were analyzed with next generation sequencing (NGS) and optical mapping. Sequence data was used for multi-locus sequence typing (MLST), phylogenetic analysis by maximum likelihood (PAML), and identification of virulence genes and single nucleotide polymorphisms (SNP) relative to reference strains.ResultsThe twelve children studied demonstrated severity of illness scores ranging from 0 (mild) to 9 (severe). All isolates were USA300, ST 8, SCC mec IVa MRSA by MLST. The isolates differed from reference strains by 2 insertions (40 Kb each) and 2 deletions (10 and 25 Kb) but had no rearrangements or copy number variations. There was a higher occurrence of virulence genes among study isolates when compared to the reference strains (p = 0.0124). There were an average of 11 nonsynonymous SNPs per strain. PAML demonstrated heterogeneity of study isolates from each other and from the reference strains.DiscussionGenomic heterogeneity exists among MRSA isolates causing osteomyelitis among children in a single community. These variations may play a role in the pathogenesis of variation in clinical severity among these children.

Cefazolin and Ertapenem, a Synergistic Combination Used To Clear Persistent Staphylococcus aureus Bacteremia

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Identification and characterization of potential membrane-bound molecular drug targets of methicillin-resistant Staphylococcus aureus using in silico approaches

“…Noteworthy, not all methicillin-resistant strains of S. aureus have either their genomes sequenced completely or proteomes annotated. Therefore, in this study we have compared annotated proteomes of already sequenced methicillin-resistant strains, namely MRSA ATCC BAA-1680 [115], H-EMRSA-15 [116], LA MRSA ST398 [117], MRSA 252 [118], ST772 MRSA [119], and UTSW MRSA 55 [120], in order to identify common sequences.…”

Procalcitonin and Pancreatic Stone Protein Function as Biomarkers in Early Diagnosis of Pediatric Acute Osteomyelitis

“…Acute osteomyelitis is usually caused by pyogenic bacteria through hematogenous infection, and MRSA [ 12 – 14 ]. Acute osteomyelitis can easily turn chronic if the onset is not recognized early, and may be complicated with sepsis, bone abnormalities, pain from repeated surgeries, and associated medical treatment costs [ 15 ].…”