Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei
Hao Chung The, Christine Boinett, Pham Thanh Duy, Claire Jenkins, Francois-Xavier Weill, Benjamin P Howden, Mary Valcanis, Niall De Lappe, Martin Cormican, Sonam Wangchuk, Ladaporn Bodhidatta, Carl J Mason, Nguyen Thi Nguyen To, Ha Thanh Tuyen, Phat Voong Vinh, Thuy Duong Vu, Huong Lan Nguyen Phu, Paul Turner, Ryan Wick, Pieter-Jan Ceyssens Show all
NATURE COMMUNICATIONS | NATURE PORTFOLIO | Published : 2019
Shigella sonnei increasingly dominates the international epidemiological landscape of shigellosis. Treatment options for S. sonnei are dwindling due to resistance to several key antimicrobials, including the fluoroquinolones. Here we analyse nearly 400 S. sonnei whole genome sequences from both endemic and non-endemic regions to delineate the evolutionary history of the recently emergent fluoroquinolone-resistant S. sonnei. We reaffirm that extant resistant organisms belong to a single clonal expansion event. Our results indicate that sequential accumulation of defining mutations (gyrA-S83L, parC-S80I, and gyrA-D87G) led to the emergence of the fluoroquinolone-resistant S. sonnei population ..View full abstract
Awarded by Wellcome Trust
Awarded by Royal Society
Awarded by French Government "Investissement d'Avenir" program (Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence)
H.C.T. received a DPhil scholarship from the Tropical Network Fund, Nuffield Department of Medicine, University of Oxford. S.B. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (100087/Z/12/Z). We thank I. Carle, M. Lejay-Collin, and C. Ruckly from the Institut Pasteur for their excellent technical assistance. F.X.W is funded by the Institut Pasteur, Sante Publique France, and by the French Government "Investissement d'Avenir" program (Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, grant no. ANR-10-LABX-62-IBEID).