Molecular epidemiology of Staphylococcus aureus bacteremia in a single large Minnesota medical center in 2015 as assessed using MLST, core genome MLST and spa typing

RESEARCH ARTICLE Molecular epidemiology of Staphylococcus aureus bacteremia in a single large Minnesota medical center in 2015 as assessed using MLST, core genome MLST and spa typing a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 Kyung-Hwa Park1,2, Kerryl E. Greenwood-Quaintance1, James R. Uhl1, Scott A. Cunningham1, Nicholas Chia3,4, Patricio R. Jeraldo3,4, Priya Sampathkumar5, Heidi Nelson3,4, Robin Patel1,5* 1 Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America, 2 Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, South Korea, 3 Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, United States of America, 4 Department of Surgery, Mayo Clinic, Rochester, Minnesota, United States of America, 5 Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America * OPEN ACCESS Citation: Park K-H, Greenwood-Quaintance KE, Uhl JR, Cunningham SA, Chia N, Jeraldo PR, et al. (2017) Molecular epidemiology of Staphylococcus aureus bacteremia in a single large Minnesota medical center in 2015 as assessed using MLST, core genome MLST and spa typing. PLoS ONE 12 (6): e0179003. https://doi.org/10.1371/journal. pone.0179003 Editor: Herminia de Lencastre, Rockefeller University, UNITED STATES Received: February 27, 2017 Accepted: May 22, 2017 Published: June 2, 2017 Copyright: © 2017 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data is within the manuscript and the NCBI Repository (BioProject number PRJNA384623) at the following URL: https://www.ncbi.nlm.nih.gov/ Traces/study/?acc=SRP105427. Abstract Staphylococcus aureus is a leading cause of bacteremia in hospitalized patients. Whether or not S. aureus bacteremia (SAB) is associated with clonality, implicating potential nosocomial transmission, has not, however, been investigated. Herein, we examined the epidemiology of SAB using whole genome sequencing (WGS). 152 SAB isolates collected over the course of 2015 at a single large Minnesota medical center were studied. Staphylococcus protein A (spa) typing was performed by PCR/Sanger sequencing; multilocus sequence typing (MLST) and core genome MLST (cgMLST) were determined by WGS. Forty-eight isolates (32%) were methicillin–resistant S. aureus (MRSA). The isolates encompassed 66 spa types, clustered into 11 spa clonal complexes (CCs) and 10 singleton types. 88% of 48 MRSA isolates belonged to spa CC-002 or -008. Methicillin-susceptible S. aureus (MSSA) isolates were more genotypically diverse, with 61% distributed across four spa CCs (CC002, CC-012, CC-008 and CC-084). By MLST, there was 31 sequence types (STs), including 18 divided into 6 CCs and 13 singleton STs. Amongst MSSA isolates, the common MLST clones were CC5 (23%), CC30 (19%), CC8 (15%) and CC15 (11%). Common MRSA clones were CC5 (67%) and CC8 (25%); there were no MRSA isolates in CC45 or CC30. By cgMLST analysis, there were 9 allelic differences between two isolates, with the remaining 150 isolates differing from each other by over 40 alleles. The two isolates were retroactively epidemiologically linked by medical record review. Overall, cgMLST analysis resulted in higher resolution epidemiological typing than did multilocus sequence or spa typing. Funding: The authors received no specific funding for this work. Competing interests: Dr. Patel reports grants from CD Diagnostics, BioFire, Check-Points, Curetis, PLOS ONE | https://doi.org/10.1371/journal.pone.0179003 June 2, 2017 1 / 12 Epidemiology of Staphylococcus aureus bacteremia Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company. Dr. Patel is a consultant to Curetis; monies are paid to Mayo Clinic. In addition, Dr. Patel has a patent on Bordetella pertussis/ parapertussis PCR issued, a patent on a device/ method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an antibiofilm substance issued. Dr. Patel serves on an Actelion data monitoring board; any reimbursement is paid to Mayo Clinic. Dr. Patel receives travel reimbursement and an editor’s stipend from ASM and IDSA, and honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Introduction Staphylococcus aureus is responsible for a high percentage of hospital- and communityacquired infections worldwide. It is also a leading cause of bacteremia, often associated with metastatic infections and significant morbidity and mortality. The epidemiology of S. aureus infection has changed over the past decade and a half, with methicillin-resistant S. aureus (MRSA) being increasingly identified in community settings. This has led to interest in attempting to understand the genetic background of the pathogen across different geographic regions and care settings [1–3]. Since a retrospective, population-based, cohort study was done to evaluate initial episodes of S. aureus bacteremia (SAB) occurring in adult residents of Olmsted County, Minnesota, from 1998 through 2005 [4], there has been little data about the epidemiology of SAB from this area, and there has been no genetic characterization of involved isolates. In hospital settings, S. aureus may be transmitted from patient to patient via healthcare worker hands, contaminated equipment or through environmental contamination. Focused infection prevention and control (IPAC) measures guided by epidemiological investigations are necessary to prevent nosocomial transmission. To inform IPAC strategies within individual institutions, it is helpful to understand the molecular epidemiology of infection, including whether particular strains are prevalent, and whether or not there is evidence of patient to patient transmission. In recent years, numerous tools have become available for typing of S. aureus, ranging from fingerprint-based methods such as pulsed-field gel electrophoresis (PFGE), to PCR-based methods such as multilocus variable-number tandem repeat analysis, to sequence-based methods such as multilocus sequencing typing (MLST), and most recently, to whole genome sequencing (WGS) [5]. The most widely used molecular typing method for defining MRSA epidemiology has traditionally been PFGE [6]. However, PFGE results can be challenging to compare between laboratories and to interpret; furthermore, PFGE is low throughput, is not suitable for long-term epidemiological investigations and assesses a limited amount of the microbial genome [7, 8]. A low mutation rate of the sequence fragments of seven housekeeping genes makes M (...truncated)