Background Shigellosis (previously bacillary dysentery) was the primary diarrhoeal disease of World War 1, but outbreaks still occur in military operations, and shigellosis causes hundreds of thousands of deaths per year in developing nations. We aimed to generate a high-quality reference genome of the historical Shigella flexneri isolate NCTC1 and to examine the isolate for resistance to antimicrobials. Methods In this genomic analysis, we sequenced the oldest extant Shigella flexneri serotype 2a isolate using single-molecule real-time (SMRT) sequencing technology. Isolated from a soldier with dysentery from the British forces fighting on the Western Front in World War 1, this bacterium, NCTC1, was the first isolate accessioned into the National Collection of Type Cultures. We created a reference sequence for NCTC1, investigated the isolate for antimicrobial resistance, and undertook comparative genetics with S flexneri reference strains isolated during the 100 years since World War 1. Findings We discovered that NCTC1 belonged to a 2a lineage of S flexneri, with which it shares common characteristics and a large core genome. NCTC1 was resistant to penicillin and erythromycin, and contained a complement of chromosomal antimicrobial resistance genes similar to that of more recent isolates. Genomic islands gained in the S flexneri 2a lineage over time were predominately associated with additional antimicrobial resistances, virulence, and serotype conversion. Interpretation This S flexneri 2a lineage is a well adapted pathogen that has continued to respond to selective pressures. We have created a valuable historical benchmark for shigellae in the form of a high-quality reference sequence for a publicly available isolate. Funding The Wellcome Trust.
Bibliographical noteFunding Information:
The Wellcome Trust Sanger Institute, of which KSB, AEM, PC, GCL, JP, and NRT are employees, has received a grant from the Wellcome Trust. JP has received travel expenses from Illumina and Pacific Biosciences. JER, AD-G, and HMcG's institution has received a grant from the Wellcome Trust. MD declares no competing interests.
We thank Claire Jenkins from the Gastrointestinal Bacteria Reference Unit, Public Health England, Colindale, for antimicrobial resistance testing and other staff at the Wellcome Trust Sanger Institute (WTSI), including David Harris, members of the sequencing teams, and other support staff. Authors from the WTSI (KSB, AEM, PC, GCL, JP, and NRT) were supported by the Wellcome Trust (grant number 098051).
© 2014 Baker et al. Open Access article distributed under the terms of CC BY.