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Whole-genome sequencing reveals the contribution of long-term carriers in staphylococcus aureus outbreak investigation

Lookup NU author(s): Professor Kate Gould

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Copyright © 2017 Gordon et al. Whole-genome sequencing (WGS) makes it possible to determine the relatedness of bacterial isolates at a high resolution, thereby helping to characterize outbreaks. However, for Staphylococcus aureus, the accumulation of within-host diversity during carriage might limit the interpretation of sequencing data. In this study, we hypothesized the converse, namely, that within-host diversity can in fact be exploited to reveal the involvement of long-term carriers (LTCs) in outbreaks. We analyzed WGS data from 20 historical outbreaks and applied phylogenetic methods to assess genetic relatedness and to estimate the time to most recent common ancestor (TMRCA). The findings were compared with the routine investigation results and epidemiological evidence. Outbreaks with epidemiological evidence for an LTC source had a mean estimated TMRCA (adjusted for outbreak duration) of 243 days (95% highest posterior density interval [HPD], 143 to 343 days) compared with 55 days (95% HPD, 28 to 81 days) for outbreaks lacking epidemiological evidence for an LTC (P < 0.004). A threshold of 156 days predicted LTC involvement with a sensitivity of 0.875 and a specificity of 1. We also found 6/20 outbreaks included isolates with differing antimicrobial susceptibility profiles; however, these had only modestly increased pairwise diversity (mean 17.5 single nucleotide variants [SNVs] [95% confidence interval {CI}, 17.3 to 17.8]) compared with isolates with identical antibiograms (12.7 SNVs [95% CI, 12.5 to 12.8]) (P < 0.0001). Additionally, for 2 outbreaks, WGS identified 1 or more isolates that were genetically distinct despite having the outbreak pulsed-field gel electrophoresis (PFGE) pulsotype. The duration-adjusted TMRCA allowed the involvement of LTCs in outbreaks to be identified and could be used to decide whether screening for long-term carriage (e.g., in health care workers) is warranted. Requiring identical antibiograms to trigger investigation could miss important contributors to outbreaks.


Publication metadata

Author(s): Gordon NC, Pichon B, Golubchik T, Wilson DJ, Paul J, Blanc DS, Cole K, Collins J, Cortes N, Cubbon M, Gould FK, Jenks PJ, Llewelyn M, Nash JQ, Orendi JM, Paranthaman K, Price JR, Senn L, Thomas HL, Wyllie S, Crook DW, Peto TEA, Walker AS, Kearns AM

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Microbiology

Year: 2017

Volume: 55

Issue: 7

Pages: 2188-2191

Print publication date: 01/07/2017

Online publication date: 03/05/2017

Acceptance date: 22/04/2017

ISSN (print): 0095-1137

ISSN (electronic): 1098-660X

Publisher: American Society for Microbiology

URL: https://doi.org/10.1128/JCM.00363-17

DOI: 10.1128/JCM.00363-17


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