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MRSA Strains with Distinct Accessory Genes Predominate at Different Ages in Cystic Fibrosis
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  • Harry Porterfield,
  • Lucas Maakestad,
  • Mason LaMarche,
  • Andrew Thurman,
  • Zoe Kienenberger,
  • Nicholas Pitcher,
  • Alexis Hansen,
  • Christian Zirbes,
  • Linda Boyken,
  • Bethany Muyskens,
  • Alejandro Pezzulo,
  • Sachinkumar Singh,
  • Erik Twait,
  • Bradley Ford,
  • Daniel Diekema,
  • Valerie Reeb,
  • Anthony Fischer
Harry Porterfield
The University of Iowa Roy J and Lucille A Carver College of Medicine

Corresponding Author:[email protected]

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Lucas Maakestad
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Mason LaMarche
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Andrew Thurman
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Zoe Kienenberger
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Nicholas Pitcher
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Alexis Hansen
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Christian Zirbes
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Linda Boyken
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Bethany Muyskens
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Alejandro Pezzulo
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Sachinkumar Singh
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Erik Twait
The University of Iowa State Hygienic Laboratory
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Bradley Ford
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Daniel Diekema
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Valerie Reeb
The University of Iowa State Hygienic Laboratory
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Anthony Fischer
The University of Iowa Roy J and Lucille A Carver College of Medicine
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Abstract

Rationale: Methicillin resistant Staphylococcus aureus (MRSA) is prevalent and consequential in cystic fibrosis (CF). Whole genome sequencing (WGS) could reveal genomic differences in MRSA associated with poorer outcomes or detect MRSA transmission. Objectives: To identify MRSA genes associated with low lung function and identify potential MRSA transmission in CF. Methods: We collected 97 MRSA isolates from 74 individuals with CF from 2017 and performed short-read WGS. We determined sequence type (ST) and the phylogenetic relationship between isolates. We aligned accessory genes from 25 reference genomes to genome assemblies. We classified the MRSA by accessory gene content and correlated the accessory genome to clinical outcomes. Results: The most prevalent ST were ST5 (N=55), ST105 (N=14), and ST8 (N=14). Closely related MRSA strains were shared by family members with CF, but rarely between unrelated individuals. Three distinct clusters of MRSA were identified by accessory genome content. The first included ST5 and ST105 strains and was common among older patients with lower FEV1. The second cluster included ST8, which was generally identified in younger patients. Sputum density of MRSA and Pseudomonas aeruginosa was higher in cultures from patients with ST5/ST105 compared to patients with ST8 at similar ages. Conclusions: In this CF cohort, we identified MRSA subtypes that predominate at different ages and differ by accessory gene content. ST5 and ST105 represented the most prevalent cluster of MRSA. ST8 MRSA was more common in younger patients and thus has the potential to rise in prevalence as these patients age.
26 Jan 2021Submitted to Pediatric Pulmonology
27 Jan 2021Submission Checks Completed
27 Jan 2021Assigned to Editor
29 Jan 2021Reviewer(s) Assigned
10 Mar 2021Review(s) Completed, Editorial Evaluation Pending
10 Mar 2021Editorial Decision: Revise Major
11 May 20211st Revision Received
12 May 2021Submission Checks Completed
12 May 2021Assigned to Editor
12 May 2021Reviewer(s) Assigned
22 Jun 2021Review(s) Completed, Editorial Evaluation Pending
22 Jun 2021Editorial Decision: Revise Minor
28 Jun 20212nd Revision Received
29 Jun 2021Submission Checks Completed
29 Jun 2021Assigned to Editor
29 Jun 2021Reviewer(s) Assigned
29 Jun 2021Review(s) Completed, Editorial Evaluation Pending
29 Jun 2021Editorial Decision: Accept