Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei

Hao Chung The, Christine Boinett, Duy Pham Thanh, Claire Jenkins, Francois-Xavier Weill, Benjamin P. Howden, Mary Valcanis, Niall De Lappe, Martin Cormican, Sonam Wangchuk, Ladaporn Bodhidatta, Carl J. Mason, To Nguyen Thi Nguyen, Tuyen Ha Thanh, Vinh Phat Voong, Vu Thuy Duong, Phu Huong Lan Nguyen, Paul Turner, Ryan Wick, Pieter-Jan Ceyssens, Guy Thwaites, Kathryn E. Holt, Nicholas R. Thomson, Maia A. Rabaa () and Stephen Baker
Additional contact information
Hao Chung The: Oxford University Clinical Research Unit
Christine Boinett: Oxford University Clinical Research Unit
Duy Pham Thanh: Oxford University Clinical Research Unit
Claire Jenkins: Public Health England
Francois-Xavier Weill: Unité des Bactéries Pathogènes Entériques
Benjamin P. Howden: The University of Melbourne
Mary Valcanis: The University of Melbourne
Niall De Lappe: University Hospital Galway
Martin Cormican: National University of Ireland Galway
Sonam Wangchuk: Royal Government of Bhutan
Ladaporn Bodhidatta: Armed Forces Research Institute of Medical Sciences
Carl J. Mason: Armed Forces Research Institute of Medical Sciences
To Nguyen Thi Nguyen: Oxford University Clinical Research Unit
Tuyen Ha Thanh: Oxford University Clinical Research Unit
Vinh Phat Voong: Oxford University Clinical Research Unit
Vu Thuy Duong: Oxford University Clinical Research Unit
Phu Huong Lan Nguyen: Oxford University Clinical Research Unit
Paul Turner: Oxford University
Ryan Wick: Monash University
Pieter-Jan Ceyssens: Unit Bacterial Diseases, Sciensano
Guy Thwaites: Oxford University Clinical Research Unit
Kathryn E. Holt: Monash University
Nicholas R. Thomson: London School of Hygiene and Tropical Medicine
Maia A. Rabaa: Oxford University Clinical Research Unit
Stephen Baker: Oxford University Clinical Research Unit

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract 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 around 2007 in South Asia. This clone was then transmitted globally, resulting in establishments in Southeast Asia and Europe. Mutation analysis suggests that the clone became dominant through enhanced adaptation to oxidative stress. Experimental evolution reveals that under fluoroquinolone exposure in vitro, resistant S. sonnei develops further intolerance to the antimicrobial while the susceptible counterpart fails to attain complete resistance.

Date: 2019
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DOI: 10.1038/s41467-019-12823-0

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