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N Engl J Med. 2014 Jan 23;370(4):334-40. doi: 10.1056/NEJMoa1308663. Epub 2014 Jan 8.

Second-pandemic strain of Vibrio cholerae from the Philadelphia cholera outbreak of 1849.

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From the McMaster Ancient DNA Centre (A.M.D., J.M.E., M.K., S.F., K.I.B., H.N.P.), Departments of Anthropology (A.M.D., M.K., K.I.B., H.N.P.), Biology (J.M.E., G.B.G., H.N.P.), and Mathematics and Statistics (D.J.D.E.), and the Michael G. DeGroote Institute for Infectious Disease Research (N.W., D.J.D.E., H.N.P.), McMaster University, Hamilton, ON, and the Dalla Lana School of Public Health, Toronto (D.N.F.) - all in Canada; the Department of Mathematics, Ohio State University, Columbus (J.H.T.); Marie Bashir Institute for Infectious Diseases and Biosecurity Institute, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney (M.S., E.C.H.); and the College of Physicians of Philadelphia, Mütter Museum, Philadelphia (A.N.D.).


In the 19th century, there were several major cholera pandemics in the Indian subcontinent, Europe, and North America. The causes of these outbreaks and the genomic strain identities remain a mystery. We used targeted high-throughput sequencing to reconstruct the Vibrio cholerae genome from the preserved intestine of a victim of the 1849 cholera outbreak in Philadelphia, part of the second cholera pandemic. This O1 biotype strain has 95 to 97% similarity with the classical O395 genome, differing by 203 single-nucleotide polymorphisms (SNPs), lacking three genomic islands, and probably having one or more tandem cholera toxin prophage (CTX) arrays, which potentially affected its virulence. This result highlights archived medical remains as a potential resource for investigations into the genomic origins of past pandemics.

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