Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
- University of Oxford, United Kingdom
- University of St Andrews, United Kingdom
- Sunpasitthiprasong Hospital, Thailand
- Mahidol University, Thailand
- University of Cambridge, United Kingdom
- Cambridge University Hospitals NHS Foundation Trust, United Kingdom
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) transmission in the hospital setting has been a frequent subject of investigation using bacterial genomes, but previous approaches have not yet fully utilised the extra deductive power provided when multiple pathogen samples are acquired from each host. Here, we use a large dataset of MRSA sequences from multiply-sampled patients to reconstruct colonisation of individuals in a high-transmission setting in a hospital in Thailand. We reconstructed transmission trees for MRSA. We also investigated transmission between anatomical sites on the same individual, finding that this either occurs repeatedly or involves a wide transmission bottleneck. We examined the between-subject bottleneck, finding a wide range in the amount of diversity transmitted. Finally, we compared our approach to the simpler method of identifying transmission pairs using single nucleotide polymorphism (SNP) counts. This suggested that the optimum threshold for identifying a pair is 39 SNPs, if sensitivities and specificities are equally weighted.
Data availability
Illumina read data is available in the European Nucleotide Archive as part of study accession number PRJEB4140. Genome assemblies will be made available prior to publication. We are unable to provide patient data for reasons of confidentiality.
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Staphylococcus aureus ST239 diversity in ThailandEuropean Nucleotide Archive, PRJEB4140.
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Evolution of MRSA During Hospital Transmission and Intercontinental SpreadEuropean Nucleotide Archive, PRJEB2489.
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Staphylococcus aureus ST239 diversityEuropean Nucleotide Archive, PRJEB2076.
Article and author information
Author details
Direk Limmathurotsakul
Funding
Wellcome (098051)
- Matthew TG Holden
- Sharon J Peacock
Chief Scientist Office (SIRN10)
- Matthew TG Holden
Wellcome (106698/Z/14/Z)
- Vanaporn Wuthiekanun
Medical Research Council (G1000803)
- Sharon J Peacock
European Research Council (PBDR-339251)
- Matthew D Hall
- Christophe Fraser
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mark Jit, London School of Hygiene & Tropical Medicine, and Public Health England, United Kingdom
Ethics
Human subjects: Ethical approval was obtained from the Ethical and Scientific Review subcommittee of the Royal Thai Government Ministry of Public Health (85/2550), and the Oxford Tropical Research Ethics Committee (024 07). All patients admitted to the two ICUs were eligible for inclusion and were enrolled after written informed consent, and consent to publish, was obtained.
Version history
- Received: February 26, 2019
- Accepted: October 1, 2019
- Accepted Manuscript published: October 8, 2019 (version 1)
- Accepted Manuscript updated: October 11, 2019 (version 2)
- Version of Record published: January 10, 2020 (version 3)
- Version of Record updated: January 14, 2020 (version 4)
Copyright
© 2019, Hall et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
eLife 8:e46402.
https://doi.org/10.7554/eLife.46402
Further reading
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- Epidemiology and Global Health
Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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- Ecology
- Epidemiology and Global Health
Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
