@article{Grandjean:2017:10.1371/journal.pone.0189838,
author = {Grandjean, L and Gilman, RH and Iwamoto, T and Köser, CU and Coronel, J and Zimic, M and Török, ME and Ayabina, D and Kendall, M and Fraser, C and Harris, S and Parkhill, J and Peacock, SJ and Moore, DAJ and Colijn, C},
doi = {10.1371/journal.pone.0189838},
journal = {PLoS ONE},
pages = {e0189838--e0189838},
title = {Convergent evolution and topologically disruptive polymorphisms among multidrug-resistant tuberculosis in Peru.},
url = {http://dx.doi.org/10.1371/journal.pone.0189838},
volume = {12},
year = {2017}
}

Download

TY  - JOUR
AB  - BACKGROUND: Multidrug-resistant tuberculosis poses a major threat to the success of tuberculosis control programs worldwide. Understanding how drug-resistant tuberculosis evolves can inform the development of new therapeutic and preventive strategies. METHODS: Here, we use novel genome-wide analysis techniques to identify polymorphisms that are associated with drug resistance, adaptive evolution and the structure of the phylogenetic tree. A total of 471 samples from different patients collected between 2009 and 2013 in the Lima suburbs of Callao and Lima South were sequenced on the Illumina MiSeq platform with 150bp paired-end reads. After alignment to the reference H37Rv genome, variants were called using standardized methodology. Genome-wide analysis was undertaken using custom written scripts implemented in R software. RESULTS: High quality homoplastic single nucleotide polymorphisms were observed in genes known to confer drug resistance as well as genes in the Mycobacterium tuberculosis ESX secreted protein pathway, pks12, and close to toxin/anti-toxin pairs. Correlation of homoplastic variant sites identified that many were significantly correlated, suggestive of epistasis. Variation in genes coding for ESX secreted proteins also significantly disrupted phylogenetic structure. Mutations in ESX genes in key antigenic epitope positions were also found to disrupt tree topology. CONCLUSION: Variation in these genes have a biologically plausible effect on immunogenicity and virulence. This makes functional characterization warranted to determine the effects of these polymorphisms on bacterial fitness and transmission.
AU  - Grandjean,L
AU  - Gilman,RH
AU  - Iwamoto,T
AU  - Köser,CU
AU  - Coronel,J
AU  - Zimic,M
AU  - Török,ME
AU  - Ayabina,D
AU  - Kendall,M
AU  - Fraser,C
AU  - Harris,S
AU  - Parkhill,J
AU  - Peacock,SJ
AU  - Moore,DAJ
AU  - Colijn,C
DO  - 10.1371/journal.pone.0189838
EP  - 0189838
PY  - 2017///
SN  - 1932-6203
SP  - 0189838
TI  - Convergent evolution and topologically disruptive polymorphisms among multidrug-resistant tuberculosis in Peru.
T2  - PLoS ONE
UR  - http://dx.doi.org/10.1371/journal.pone.0189838
UR  - http://hdl.handle.net/10044/1/55584
VL  - 12
ER  - 

Download