Evans, Daniel R
(2021)
Genomic Epidemiology of Horizontal Plasmid Transfer Among
Healthcare-Associated Bacterial Pathogens in a Tertiary Hospital.
Master's Thesis, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Healthcare-associated bacterial pathogens frequently carry plasmids that contribute to antibiotic resistance and virulence. The horizontal transfer of plasmids between pathogens within hospitals has been previously documented, but the epidemiology and clinical burden of nosocomial plasmid transfer remains poorly understood. Our primary objective was to systematically resolve plasmids from whole-genome sequences of nosocomial bacterial isolates, using thresholds of sequence similarity that were indicative of horizontal transfer. Our secondary objective was to identify potential routes and assess the clinical burden of horizontal plasmid transfer.
Whole-genome sequencing was performed on 3,074 nosocomial bacterial isolates from 2,322 hospitalizations of 1,960 patients, using the Illumina platform. Seventy-eight strains were also sequenced by long-read Oxford Nanopore technology, and hybrid genome assemblies were generated using Unicycler. Plasmids were resolved from Illumina-sequenced genomes by alignment using BLASTn. Single nucleotide polymorphisms (SNPs) were identified using Snippy. De-identified patient data associated with bacterial isolates – including length of hospital stay and Charlson comorbidity index – were collected using Theradoc.
Ninety-five percent of analyzed strains maintained at least 95% of the sequence content of reference plasmids, with SNPs occurring at rates of fewer than 1 per 5000bp of reference plasmid sequence. Using these thresholds, we identified 41 plasmid lineages that were potentially horizontally transferred among non-clonal bacterial strains. Of these lineages, 28 (68.2%) were significantly associated with at least one medical procedure, room, or hospital ward. Hospitalizations involving the 41 plasmid lineages were significantly longer (+3 days; 95% CI +1 to +4; p < 0.001) than hospitalizations not involving those plasmids. Patients infected with strains carrying transferred plasmids had significantly greater overall comorbidity (Charlson comorbidity index +1, 95% CI +1 to +2; p < 0.0001) than patients whose infections did not involve plasmids in lineages.
Our findings show that the horizontal transfer of plasmids among bacterial isolates causing nosocomial infections is frequent, and that this phenomenon may impose an unappreciated clinical burden by exacerbating infections by isolates carrying these plasmids. Future directions will include more detailed analyses of comorbidity and mortality, as well as sequencing of additional samples to confirm or refute hypothesized routes of plasmid transfer.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
10 May 2021 |
| Date Type: |
Publication |
| Defense Date: |
5 April 2021 |
| Approval Date: |
10 May 2021 |
| Submission Date: |
8 April 2021 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
85 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
genomics, epidemiology, healthcare-associated infections, plasmids, bacteria, mobile genetic elements, horizontal gene transfer |
| Date Deposited: |
10 May 2021 23:51 |
| Last Modified: |
10 May 2021 23:51 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/40835 |
Available Versions of this Item
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Genomic Epidemiology of Horizontal Plasmid Transfer Among
Healthcare-Associated Bacterial Pathogens in a Tertiary Hospital. (deposited 10 May 2021 23:51)
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