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, United Kingdom
Figures
Figure 1
50% majority-rule consensus tree of the posterior distribution of ExaBayes phylogenies.
Branch lengths are in substitutions per site. Eight clades are highlighted. Clades 1 to 5 correspond to those identified by Tong et al. (2015), while the additional three are newly designated.
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Figure 1—source data 1
ExaBayes consensus tree in Newick format.
- https://cdn.elifesciences.org/articles/46402/elife-46402-fig1-data1-v4.zip
Figure 2 with 1 supplement
The median number of SNPs separating sequences from each colonisation from the most similar sequence from an isolate acquired before the date of the first positive sample from that colonisation.
Blue dots are colonisations isolated from a single swab only (trace colonisations), while red were acquired from colonisations where multiple swabs were isolated. For three colonisations (two trace) …
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Figure 2—source data 1
Source data and R script for creation of Figure 2 and Figure 2—figure supplement 1.
- https://cdn.elifesciences.org/articles/46402/elife-46402-fig2-data1-v4.zip
Figure 2—figure supplement 1
The median number of SNPs separating sequences from each colonisation, restricted to those obtained at the time of the first positive swab, from the most similar sequence from an isolate acquired before the date of the first positive sample from that colonisation.
Blue dots are colonisations isolated from a single swab only (trace colonisations), while red were acquired from colonisations where multiple swabs were isolated. For three colonisations (two trace) …
Figure 3
phyloscanner identifies transmission pairs by ancestral state reconstruction of hosts (left) and subsequent classification of the topological relationships between the subgraphs reconstructed to each host (right).
In this example the hosts are designated (A to D). Here host A is inferred to be the infector of hosts (B and C). The transmission from (A to C) was of only a single pathogen lineage, while that …
Figure 4 with 1 supplement
The reconstruction of the transmission process using the consensus tree overlaid on a timeline of hospital and ICU stays and sampling events.
Each row represents a colonisation, with thin lines representing the colonised subject’s presence in the hospital and thick lines their presence as a patient in an ICU. Colours of the lines and the y…
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Figure 4—source data 1
Source data and R script for creation of Figure 4 and Figure 4—figure supplement 1.
- https://cdn.elifesciences.org/articles/46402/elife-46402-fig4-data1-v4.zip
Figure 4—figure supplement 1
The reconstruction of the transmission process using the consensus tree overlaid on a timeline of hospital and ICU stays and sampling events, with trace colonisations included.
Each row represents a colonisation, with thin lines representing the colonised subject’s presence in the hospital and thick lines their presence as a patient in an ICU. Colours of the lines and the y…
Figure 5 with 2 supplements
Concordance of inferred infectors for each colonisation with recorded timings of hospital stays and sampling dates.
Each bar represents a colonisation, and the colours represent the proportions of the posterior set of trees where the transmission chain prior to that host involves no sampled subjects (blue), …
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Figure 5—source data 1
Source data and R scripts for creation of Figure 5, Figure 5—figure supplement 1 and Figure 5—figure supplement 2.
- https://cdn.elifesciences.org/articles/46402/elife-46402-fig5-data1-v4.zip
Figure 5—figure supplement 1
Concordance of inferred infectors for each colonisation with recorded timings of hospital stays and sampling dates, with trace colonisations included.
Each bar represents a colonisation, and the colours represent the proportions of the posterior set of trees where the transmission chain prior to that host involves no sampled subjects (blue), …
Figure 5—figure supplement 2
Concordance of inferred infectors for each colonisation with recorded timings of hospital stays and sampling dates, from a secondary phyloscanner analysis in which the tip set from each subject was randomly downsampled until a maximum of five remained.
Each bar represents a colonisation, and the colours represent the proportions of the posterior set of trees where the transmission chain prior to that host involves no sampled subjects (blue), …
Figure 6 with 1 supplement
The phyloscanner host relationship diagram.
Each node represents all the sequences for one colonisation. Node fill colours designate patients in the two hospital ICUs and the HCWs. Edges appear where colonisations share a relationship with …
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Figure 6—source data 1
Source data and R script for creation of Figure 6 and Figure 6—figure supplement 1.
- https://cdn.elifesciences.org/articles/46402/elife-46402-fig6-data1-v4.zip
Figure 6—figure supplement 1
The phyloscanner host relationship diagram, with trace colonisations included.
Each node represents all the sequences for one colonisation. Node fill colours designate patients in the two hospital ICUs and the HCWs and nodes with faded colours representing trace colonisations. …
Figure 7 with 1 supplement
The phyloscanner host relationship diagram for a separate analysis where samples taken from distinct body sites on the same subject were treated as separate ‘hosts’.
Each node represents all the sequences for one colonisation of one body site. Node fill colours designate patients in the two hospital ICUs and the HCWs. Edges appear where colonisations share a …
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Figure 7—source data 1
Source data and R script for creation of Figure 7 and Figure 7—figure supplement 1.
- https://cdn.elifesciences.org/articles/46402/elife-46402-fig7-data1-v4.zip
Figure 7—figure supplement 1
The phyloscanner host relationship diagram for the body site analysis, with trace colonisations included.
Each node represents all the sequences for one colonisation of one body site. Node fill colours designate patients in the two hospital ICUs and the HCWs and nodes with faded colours representing …
Figure 8
50% majority-rule consensus phylogenies for the ExaBayes phylogenetic analyses of the sequences from patients T009, T126, T232 and T249.
Tips are coloured by body site of origin. Branch lengths are in substitutions per site. Trees were rooted using the TW20 outgroup (not shown).
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Figure 8—source data 1
ExaBayes consensus trees for all subjects analysed in the phyloanatomy analysis.
- https://cdn.elifesciences.org/articles/46402/elife-46402-fig8-data1-v4.zip
Figure 9 with 1 supplement
Performance of SNP distance as a method for identifying transmission pairs.
(A) Plots of the sensitivity and specificity of using the number of SNPs to identify transmission pairs, for different distance thresholds. (B) ROC curves plotting true positive rate (sensitivity) …
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Figure 9—source data 1
Source data and R script for creation of Figure 9 and Figure 9—figure supplement 1.
- https://cdn.elifesciences.org/articles/46402/elife-46402-fig9-data1-v4.zip
Figure 9—figure supplement 1
Plots of the sensitivity and specificity of using the number of SNPs to identify transmission pairs, for different distance thresholds.
The gold standard for identifying transmission pairs in the version on the left is a topological relationship suggesting at least one transmitted lineage, while on the right at least two are …
Tables
Table 1
Six pairs of colonisations for whom transmission was reconstructed with a posterior score of at least 0.95 and, for those reconstructed transmissions, a posterior median of at least five tips were in the recipient subgraphs.
Each row gives the posterior median and the limits of the 95% highest posterior density (HPD) interval for the number of reconstructed transmissions between the subjects, in either direction. The …
| Colonisation A | Colonisation B | Number of A to B transitions 95 % HPD | Tips in descendant B subgraphs (median) | Nucleotide diversity transmitted to B (median) | Number of B to A transitions 95% HPD | Tips in descendant A subgraphs (median) | Nucleotide diversity transmitted to A (median) | Direction | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Median | Lower | Upper | Median | Lower | Upper | |||||||
| C012 | C137 | 3 | 2 | 3 | 79 | 1.46E-06 | 0 | 0 | 0 | 0 | NA | A to B |
| C012 | C159b | 34 | 25 | 38 | 39 | 2.20E-06 | 1 | 0 | 6 | 1 | 1.40E-06 | A to B |
| C126 | C234 | 3 | 3 | 3 | 10 | 1.92E-06 | 0 | 0 | 0 | 0 | NA | A to B |
| C126 | C271a | 1 | 1 | 1 | 21 | 3.11E-07 | 0 | 0 | 0 | 0 | NA | A to B |
| C126 | C327a | 5 | 4 | 5 | 9 | 2.68E-06 | 0 | 0 | 0 | 0 | NA | A to B |
| C183 | C194 | 15 | 1 | 23 | 31 | 3.41E-07 | 5 | 0 | 19 | 12 | 7.08E-07 | Unclear |
Table 2
Results of the investigation of body site/phylogeny associations.
Each row corresponds to a single BATS analysis on a posterior set of phylogenies consisting just of the sequences from that subject. The p-values are given for the association index (AI), parsimony …
| Subject | Number of Sequences | p-value | ||||||
|---|---|---|---|---|---|---|---|---|
| AI | PS | MC | ||||||
| Axilla | Nose | Throat | Trachea | Wound | ||||
| T009 | 31 | 0.026 | 1 | 1* | 0.031 | 1 | ||
| T012 | 223 | 0.24 | 0.18 | 1 | 1 | 0.14 | ||
| T065 | 11 | <0.001 | 1* | 0.29 | 1* | |||
| T071 | 13 | 0.16 | 1 | 0.16 | 1 | |||
| T092 | 12 | 0.035 | 1 | 1 | 1 | |||
| T095 | 11 | 0.099 | 1* | 0.1 | 1* | |||
| T099 | 19 | 1 | 1* | 0.16 | 1* | |||
| T126 | 239 | <0.001 | <0.001 | 0.004 | 0.1 | 0.004 | 1* | |
| T137 | 79 | 0.004 | 1 | 0.12 | 1 | 1* | ||
| T159 | 46 | 0.7 | 1 | 1* | 1 | 1 | ||
| T183 | 48 | 0.04 | 1 | 1* | 0.22 | 1 | ||
| T188 | 19 | 1 | 1* | 1 | 1* | |||
| T194 | 32 | 0.13 | 1 | 1* | 1 | 0.37 | 1* | 1* |
| T197 | 35 | 0.74 | 1 | 1 | 1 | 1 | 1 | |
| T232 | 11 | <0.001 | <0.001 | 0.001 | 0.001 | |||
| T234 | 10 | 1 | 1* | 1 | 1* | |||
| T249 | 14 | 0.002 | <0.001 | 0.017 | 0.016 | 1 | ||
| T271 | 23 | 0.043 | 1 | 1* | 0.49 | 1 | 1* | 1* |
| T327 | 10 | 1 | 1* | 0.51 | 1* | |||
| T330 | 8 | 1 | 1* | 0.26 | 1* | |||
| T358 | 22 | 0.004 | 1 | 0.06 | 1 | |||
Additional files
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Supplementary file 1
Examples of arrangements of tips with two states (red and blue) on a phylogeny and the corresponding values of the AI, PS, and MC statistics.
Given are the values of the statistic and p-values estimated by permuting the tip states 1000 times. (A) Blue tips occur only in one clade but that clade is not exclusively blue. The AI statistic shows significant deviation from the null hypothesis of no phylogeny-state association, but the others do not. (B) Blue tips form a single clade. All statistics other than the MC for the red state show significant deviation from the null. (C) Blue tips appear randomly in the phylogeny. There is no evidence of any association using any statistic. (D) A single blue tip is basal to the remainder of the tree. The AI statistic and the MC for the red state suggest an association. (E/F) A single blue tip occurs amongst the red tips. Some evidence of association may still be identified using the AI statistic and further investigation is warranted. In cases D-F the PS and MC (blue) statistics are always equal to 1.
- https://cdn.elifesciences.org/articles/46402/elife-46402-supp1-v4.docx
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Supplementary file 2
Coordinates of the accessory regions of the TW20 chromosome.
- https://cdn.elifesciences.org/articles/46402/elife-46402-supp2-v4.docx
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Supplementary file 3
Coordinates of regions of the MRSA genome in which recombination was identified by Gubbins.
Positions are with respect to the TW20 reference strain.
- https://cdn.elifesciences.org/articles/46402/elife-46402-supp3-v4.docx
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Transparent reporting form
- https://cdn.elifesciences.org/articles/46402/elife-46402-transrepform-v4.docx
