The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis
Background: Children with acute hematogenous osteomyelitis (AHO) have a broad spectrum of illness ranging from mild to severe. The purpose of this study is to evaluate the impact of genomic variation of Staphylococcus aureus on clinical phenotype of affected children and determine which virulence ge...
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doaj-4353ffe206f8417cac393639c3beba9e2020-11-25T02:58:13ZengElsevierHeliyon2405-84402018-06-0146e00674The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitisAngela Collins0Edward K. Wakeland1Prithvi Raj2Min S. Kim3Jiwoong Kim4Naureen G. Tareen5Lawson A.B. Copley6McLaren Medical Center, Department of Orthopaedic Surgery, Flint, Michigan, USAUniversity of Texas Southwestern, Department of Immunology, Dallas, Texas, USAUniversity of Texas Southwestern, Department of Immunology, Dallas, Texas, USAUniversity of Texas Southwestern, Department of Clinical Science, Dallas, Texas, USAUniversity of Texas Southwestern, Department of Clinical Science, Dallas, Texas, USAChildren's Health System of Texas, Department of Orthopaedic Surgery, Dallas, Texas, USA; Corresponding authors.University of Texas Southwestern, Department of Orthopaedic Surgery, Dallas, Texas, USA; Corresponding authors.Background: Children with acute hematogenous osteomyelitis (AHO) have a broad spectrum of illness ranging from mild to severe. The purpose of this study is to evaluate the impact of genomic variation of Staphylococcus aureus on clinical phenotype of affected children and determine which virulence genes correlate with severity of illness. Methods: De novo whole genome sequencing was conducted for a strain of Community Acquired Methicillin Resistant Staphylococcus aureus (CA-MRSA), using PacBio Hierarchical Genome Assembly Process (HGAP) from 6 Single Molecule Real Time (SMRT) Cells, as a reference for DNA library assembly of 71 Staphylococcus aureus isolates from children with AHO. Virulence gene annotation was based on exhaustive literature review and genomic data in NCBI for Staphylococcus aureus. Clinical phenotype was assessed using a validated severity score. Kruskal-Wallis rank sum test determined association between clinical severity and virulence gene presence using False Discovery Rate (FDR), significance <0.01. Results: PacBio produced an assembled genome of 2,898,306 bp and 2054 Open Reading Frames (ORFs). Annotation confirmed 201 virulence genes. Statistical analysis of gene presence by clinical severity found 40 genes significantly associated with severity of illness (FDR ≤0.009). MRSA isolates encoded a significantly greater number of virulence genes than did MSSA (p < 0.0001). Phylogenetic analysis by maximum likelihood (PAML) demonstrated the relatedness of genomic distance to clinical phenotype. Conclusions: The Staphylococcus aureus genome contains virulence genes which are significantly associated with severity of illness in children with osteomyelitis. This study introduces a novel reference strain and detailed annotation of Staphylococcus aureus virulence genes. While this study does not address bacterial gene expression, a platform is created for future transcriptome investigations to elucidate the complex mechanisms involved in childhood osteomyelitis.http://www.sciencedirect.com/science/article/pii/S2405844018306479MicrobiologyPediatricsPathologyInfectious diseaseGeneticsImmunology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Angela Collins Edward K. Wakeland Prithvi Raj Min S. Kim Jiwoong Kim Naureen G. Tareen Lawson A.B. Copley |
spellingShingle |
Angela Collins Edward K. Wakeland Prithvi Raj Min S. Kim Jiwoong Kim Naureen G. Tareen Lawson A.B. Copley The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis Heliyon Microbiology Pediatrics Pathology Infectious disease Genetics Immunology |
author_facet |
Angela Collins Edward K. Wakeland Prithvi Raj Min S. Kim Jiwoong Kim Naureen G. Tareen Lawson A.B. Copley |
author_sort |
Angela Collins |
title |
The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis |
title_short |
The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis |
title_full |
The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis |
title_fullStr |
The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis |
title_full_unstemmed |
The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis |
title_sort |
impact of staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis |
publisher |
Elsevier |
series |
Heliyon |
issn |
2405-8440 |
publishDate |
2018-06-01 |
description |
Background: Children with acute hematogenous osteomyelitis (AHO) have a broad spectrum of illness ranging from mild to severe. The purpose of this study is to evaluate the impact of genomic variation of Staphylococcus aureus on clinical phenotype of affected children and determine which virulence genes correlate with severity of illness. Methods: De novo whole genome sequencing was conducted for a strain of Community Acquired Methicillin Resistant Staphylococcus aureus (CA-MRSA), using PacBio Hierarchical Genome Assembly Process (HGAP) from 6 Single Molecule Real Time (SMRT) Cells, as a reference for DNA library assembly of 71 Staphylococcus aureus isolates from children with AHO. Virulence gene annotation was based on exhaustive literature review and genomic data in NCBI for Staphylococcus aureus. Clinical phenotype was assessed using a validated severity score. Kruskal-Wallis rank sum test determined association between clinical severity and virulence gene presence using False Discovery Rate (FDR), significance <0.01. Results: PacBio produced an assembled genome of 2,898,306 bp and 2054 Open Reading Frames (ORFs). Annotation confirmed 201 virulence genes. Statistical analysis of gene presence by clinical severity found 40 genes significantly associated with severity of illness (FDR ≤0.009). MRSA isolates encoded a significantly greater number of virulence genes than did MSSA (p < 0.0001). Phylogenetic analysis by maximum likelihood (PAML) demonstrated the relatedness of genomic distance to clinical phenotype. Conclusions: The Staphylococcus aureus genome contains virulence genes which are significantly associated with severity of illness in children with osteomyelitis. This study introduces a novel reference strain and detailed annotation of Staphylococcus aureus virulence genes. While this study does not address bacterial gene expression, a platform is created for future transcriptome investigations to elucidate the complex mechanisms involved in childhood osteomyelitis. |
topic |
Microbiology Pediatrics Pathology Infectious disease Genetics Immunology |
url |
http://www.sciencedirect.com/science/article/pii/S2405844018306479 |
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