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The TB-ARC project is a massive international collaboration, bringing together researchers and data from several continents from across the globe.  In an effort to identify the full complement of naturally occurring mutations responsible for drug resistance in clinical Mycobacterium tuberculosis, we sequenced over 1,800 geographically and phenotypically diverse isolates that have been quantitatively characterized for their resistance to a broad spectrum of first and second line antibiotics.  We identified, and experimentally validated, novel mutations (and mutation combinations) that explain previously unexplained, low frequency resistance to first and second line drugs, including cycloserine.  We have also shown that, in some countries where drug resistant tuberculosis (DR-TB) is epidemic, resistance emerged at the very beginning of the antibiotic era and that these early mutations have persisted for decades within M. tuberculosis populations and now account for a large fraction of today's DR-TB.

Collaborators

The Ó³»­´«Ã½ of Harvard and M.I.T.	Ashlee Earl, Abigail L Manson, Thomas Abeel, Christopher Desjardins, Sinead Chapman, Bruce Birren
Brigham and Women's Hospital	Keira Cohen
The Public Health Agency of Sweden, Sweden	Pontus Jureen, Sven Hoffner
Harvard T. H. Chan School of Public Health, Boston, MA, USA	Helen Jenkins
Yale School of Public Health	Theodore Cohen
Republican Research and Practical Centre for Pulmonology and Tuberculosis, Belarus	Alena Skrahina, Aksana Zalutskaya
Office of Cyber Infrastructure and Computational Biology (OCICB), National Institute of Health, USA	Andrei Gabrielian, Alex Rosenthal
Microbiology & Morphology Laboratory Phthisiopneumology Institute; Chisinau, Moldova	Valeriu Crudu
Rutgers-New Jersey Medical School, New Jersey, USA	David Alland
Johns Hopkins University, Baltimore, MD, USA	Derek Armstrong, Susan E. Dorman, William R. Bishai, Kathryn Winglee
Boston Medical Center, Boston, MA, USA	Jerrold Ellner
Makerere University College, Uganda	Willy Ssengooba
KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), South Africa	Alexander Pym
International Tuberculosis Research Center (ITRC), South Korea	Jong Seok Lee
Boston University, Boston, MA, USA	James Galagan
National Taiwan University Hospital, Taiwan	Po-Ren Hsueh
National Institute for Research in Tuberculosis (NIRT), India	Soumya Swaminathan, Sujatha Narayanan
National Institute of Allergy and Infectious disease (NIAID), National Institute of Health, USA	Maiga Mamoudou
Medical Research Council, South Africa	Marti Van der Walt, Jeannette Brand, Lesibana Malinga
TB Resist	Gail Cassell