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.
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No competing interests reported.
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Posted 10 Mar, 2021
On 12 Apr, 2021
Received 09 Apr, 2021
On 29 Mar, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
Invitations sent on 08 Feb, 2021
On 08 Feb, 2021
On 28 Jan, 2021
On 28 Jan, 2021
On 24 Jan, 2021
Posted 10 Mar, 2021
On 12 Apr, 2021
Received 09 Apr, 2021
On 29 Mar, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
Received 16 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
On 09 Feb, 2021
Invitations sent on 08 Feb, 2021
On 08 Feb, 2021
On 28 Jan, 2021
On 28 Jan, 2021
On 24 Jan, 2021
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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