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Research Article
Darío García de Viedma
Hospital General Universitario Gregorio Marañón
Corresponding Author
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Whole genome sequencing (WGS) is able to differentiate closely related Mycobacterium tuberculosis variants within the same transmission cluster. Our aim was to evaluate if this higher discriminatory power may help identify and characterize more actively transmitted variants and understand the factors behind their success. We selected a robust MIRU-VNTR-defined cluster from Almería, Spain (22 cases throughout 2003–2019). WGS allowed discriminating, within the same epidemiological setting, between a successfully transmitted variant and seven closely related variants that did not lead to secondary cases, or were involved in self-limiting transmission (one single secondary case). Intramacrophagic growth of representative variants was evaluated in an in vitro infection model using U937 cells. Growth rates were higher for the actively transmitted variant (range: 5.3–10.7) than for the unsuccessfully transmitted closely related variants (1.5–3.95). Two SNPs, mapping at the DNA binding domain of DnaA and at kdpD ,were found to be specific of the successful variant.
Keywords
Tuberculosis, transmission, infectivity
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No competing interests reported.
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Reviewer #13 agreed
On 09 Feb, 2021
Reviewer #6 agreed
On 09 Feb, 2021
Reviewer #4 agreed
On 09 Feb, 2021
Reviewer #3 agreed
On 09 Feb, 2021
Reviewer #14 agreed
On 09 Feb, 2021
Reviewer #12 agreed
On 09 Feb, 2021
Reviewer #17 agreed
On 09 Feb, 2021
Reviewer #7 agreed
On 09 Feb, 2021
Reviewer #15 agreed
On 09 Feb, 2021
Reviewer #1 agreed
On 09 Feb, 2021
Reviewer #16 agreed
On 09 Feb, 2021
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Darío García de Viedma
Hospital General Universitario Gregorio Marañón
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 10 Mar, 2021
No community comments so far
Editorial decision: Major revision
On 12 Apr, 2021
Review #2 received
Received 09 Apr, 2021
Reviewer #2 agreed
On 29 Mar, 2021
Review #10 received
Received 16 Feb, 2021
Review #3 received
Received 16 Feb, 2021
Review #1 received
Received 16 Feb, 2021
Review #11 received
Received 16 Feb, 2021
Review #9 received
Received 16 Feb, 2021
Review #14 received
Received 16 Feb, 2021
Review #4 received
Received 16 Feb, 2021
Review #12 received
Received 16 Feb, 2021
Review #13 received
Received 16 Feb, 2021
Reviewer #13 agreed
On 09 Feb, 2021
Reviewer #6 agreed
On 09 Feb, 2021
Reviewer #4 agreed
On 09 Feb, 2021
Reviewer #3 agreed
On 09 Feb, 2021
Reviewer #14 agreed
On 09 Feb, 2021
Reviewer #12 agreed
On 09 Feb, 2021
Reviewer #17 agreed
On 09 Feb, 2021
Reviewer #7 agreed
On 09 Feb, 2021
Reviewer #15 agreed
On 09 Feb, 2021
Reviewer #1 agreed
On 09 Feb, 2021
Reviewer #16 agreed
On 09 Feb, 2021
Reviewers invited
Invitations sent on 08 Feb, 2021
Editor assigned
On 08 Feb, 2021
Editor invited
On 28 Jan, 2021
Submission checks complete
On 28 Jan, 2021
First submitted
On 24 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Whole genome sequencing (WGS) is able to differentiate closely related Mycobacterium tuberculosis variants within the same transmission cluster. Our aim was to evaluate if this higher discriminatory power may help identify and characterize more actively transmitted variants and understand the factors behind their success. We selected a robust MIRU-VNTR-defined cluster from Almería, Spain (22 cases throughout 2003–2019). WGS allowed discriminating, within the same epidemiological setting, between a successfully transmitted variant and seven closely related variants that did not lead to secondary cases, or were involved in self-limiting transmission (one single secondary case). Intramacrophagic growth of representative variants was evaluated in an in vitro infection model using U937 cells. Growth rates were higher for the actively transmitted variant (range: 5.3–10.7) than for the unsuccessfully transmitted closely related variants (1.5–3.95). Two SNPs, mapping at the DNA binding domain of DnaA and at kdpD ,were found to be specific of the successful variant.
Figure 1
Figure 2
Figure 3
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