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Genomic Epidemiology of Horizontal Plasmid Transfer Among Healthcare-Associated Bacterial Pathogens in a Tertiary Hospital

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 (Unpublished)

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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:
CreatorsEmailPitt UsernameORCID
Evans, Daniel Rdre16@pitt.edudre16
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairVan Tyne, Daria Nvantyne@pitt.eduvantyne
Committee MemberHarrison, Lee Hlharriso@edc.pitt.edulharriso
Committee MemberMartinson, Jeremyjmartins@pitt.edujmartins
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: Graduate 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

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