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 Bath, United Kingdom
- 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.
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.
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:
The role of circulating metabolites on child development is understudied. We investigated associations between children’s serum metabolome and early childhood development (ECD).
Methods:
Untargeted metabolomics was performed on serum samples of 5004 children aged 6–59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children’s milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥1. The interaction between significant metabolites and the child’s age was tested.
Results:
Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child’s nutritional status, diet quality, and infant age. Cresol sulfate (β=–0.07; adjusted-p <0.001), hippuric acid (β=–0.06; adjusted-p <0.001), phenylacetylglutamine (β=–0.06; adjusted-p <0.001), and trimethylamine-N-oxide (β=–0.05; adjusted-p=0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged –1 SD: β=–0.05; pP=0.01;+1 SD: β=0.05; p=0.02) and methylhistidine (–1 SD: β = - 0.04; p=0.04;+1 SD: β=0.04; p=0.03).
Conclusions:
Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding:
Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Several areas of the world suffer a notably high incidence of Shiga toxin-producing Escherichia coli. To assess the impact of persistent cross-species transmission systems on the epidemiology of E. coli O157:H7 in Alberta, Canada, we sequenced and assembled E. coli O157:H7 isolates originating from collocated cattle and human populations, 2007–2015. We constructed a timed phylogeny using BEAST2 using a structured coalescent model. We then extended the tree with human isolates through 2019 to assess the long-term disease impact of locally persistent lineages. During 2007–2015, we estimated that 88.5% of human lineages arose from cattle lineages. We identified 11 persistent lineages local to Alberta, which were associated with 38.0% (95% CI 29.3%, 47.3%) of human isolates. During the later period, six locally persistent lineages continued to be associated with human illness, including 74.7% (95% CI 68.3%, 80.3%) of reported cases in 2018 and 2019. Our study identified multiple locally evolving lineages transmitted between cattle and humans persistently associated with E. coli O157:H7 illnesses for up to 13 y. Locally persistent lineages may be a principal cause of the high incidence of E. coli O157:H7 in locations such as Alberta and provide opportunities for focused control efforts.
