Imperial College London
Alternate

Professor Francis Drobniewski

Faculty of Medicine, Department of Infectious Disease

Chair in Global Health and Tuberculosis
 
 
 
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Contact

 

f.drobniewski

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Dixit:2019:10.1038/s41598-019-41967-8,
author = {Dixit, A and Freschi, L and Vargas, R and Calderon, R and Sacchettini, J and Drobniewski, F and Galea, JT and Contreras, C and Yataco, R and Zhang, Z and Lecca, L and Kolokotronis, S-O and Mathema, B and Farhat, MR},
doi = {10.1038/s41598-019-41967-8},
journal = {Scientific Reports},
title = {Whole genome sequencing identifies bacterial factors affecting transmission of multidrug-resistant tuberculosis in a high-prevalence setting},
url = {http://dx.doi.org/10.1038/s41598-019-41967-8},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Whole genome sequencing (WGS) can elucidate Mycobacterium tuberculosis (Mtb) transmission patterns but more data is needed to guide its use in high-burden settings. In a household-based TB transmissibility study in Peru, we identified a large MIRU-VNTR Mtb cluster (148 isolates) with a range of resistance phenotypes, and studied host and bacterial factors contributing to its spread. WGS was performed on 61 of the 148 isolates. We compared transmission link inference using epidemiological or genomic data and estimated the dates of emergence of the cluster and antimicrobial drug resistance (DR) acquisition events by generating a time-calibrated phylogeny. Using a set of 12,032 public Mtb genomes, we determined bacterial factors characterizing this cluster and under positive selection in other Mtb lineages. Four of the 61 isolates were distantly related and the remaining 57 isolates diverged ca. 1968 (95%HPD: 1945–1985). Isoniazid resistance arose once and rifampin resistance emerged subsequently at least three times. Emergence of other DR types occurred as recently as within the last year of sampling. We identified five cluster-defining SNPs potentially contributing to transmissibility. In conclusion, clusters (as defined by MIRU-VNTR typing) may be circulating for decades in a high-burden setting. WGS allows for an enhanced understanding of transmission, drug resistance, and bacterial fitness factors.
AU  - Dixit,A
AU  - Freschi,L
AU  - Vargas,R
AU  - Calderon,R
AU  - Sacchettini,J
AU  - Drobniewski,F
AU  - Galea,JT
AU  - Contreras,C
AU  - Yataco,R
AU  - Zhang,Z
AU  - Lecca,L
AU  - Kolokotronis,S-O
AU  - Mathema,B
AU  - Farhat,MR
DO  - 10.1038/s41598-019-41967-8
PY  - 2019///
SN  - 2045-2322
TI  - Whole genome sequencing identifies bacterial factors affecting transmission of multidrug-resistant tuberculosis in a high-prevalence setting
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-019-41967-8
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000463179300007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/69732
VL  - 9
ER  -
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