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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039886/ https://www.ncbi.nlm.nih.gov/pubmed/30003165 http://dx.doi.org/10.1016/j.heliyon.2018.e00674 |
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author | Collins, Angela Wakeland, Edward K. Raj, Prithvi Kim, Min S. Kim, Jiwoong Tareen, Naureen G. Copley, Lawson A.B. |
author_facet | Collins, Angela Wakeland, Edward K. Raj, Prithvi Kim, Min S. Kim, Jiwoong Tareen, Naureen G. Copley, Lawson A.B. |
author_sort | Collins, Angela |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6039886 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-60398862018-07-12 The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis Collins, Angela Wakeland, Edward K. Raj, Prithvi Kim, Min S. Kim, Jiwoong Tareen, Naureen G. Copley, Lawson A.B. Heliyon Article 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. Elsevier 2018-06-29 /pmc/articles/PMC6039886/ /pubmed/30003165 http://dx.doi.org/10.1016/j.heliyon.2018.e00674 Text en © 2018 The Authors. Published by Elsevier Ltd. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Collins, Angela Wakeland, Edward K. Raj, Prithvi Kim, Min S. Kim, Jiwoong Tareen, Naureen G. Copley, Lawson A.B. The impact of Staphylococcus aureus genomic variation on clinical phenotype of children with acute hematogenous osteomyelitis |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039886/ https://www.ncbi.nlm.nih.gov/pubmed/30003165 http://dx.doi.org/10.1016/j.heliyon.2018.e00674 |
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