Journal article

Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

Jody Phelan, Francesc Coll, Ruth McNerney, David B Ascher, Douglas EV Pires, Nick Furnham, Nele Coeck, Grant A Hill-Cawthorne, Mridul B Nair, Kim Mallard, Andrew Ramsay, Susana Campino, Martin L Hibberd, Arnab Pain, Leen Rigouts, Taane G Clark



BACKGROUND: Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. METHODS: To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide ap..

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Awarded by NHMRC CJ Martin Fellowship

Awarded by Medical Research Council Methodology Research Fellowship

Awarded by Medical Research Council UK

Awarded by MRC

Awarded by Biotechnology and Biological Sciences Research Council

Awarded by Medical Research Council

Funding Acknowledgements

JP is supported by a BBSRC PhD studentship. The project was supported by the KAUST faculty baseline research fund (KAUST-BRF) to AP. The authors wish to thank members of KAUST Bioscience Core laboratory who sequenced the isolate DNA. DBA is supported by an NHMRC CJ Martin Fellowship (APP1072476). DEVP is supported by Rene Rachou Research Center (CPqRR/FIOCRUZ Minas). DBA and DEVP are funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG). NF is funded by a Medical Research Council Methodology Research Fellowship (MR//K020420). TGC is funded by the Medical Research Council UK (Grant no. MR/K000551/1, MR/M01360X/1, MR/N010469/1). There are no conflicts of interests.