%0 Journal Article %J Nat Commun %D 2019 %T Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei. %A Chung The, Hao %A Christine Boinett %A Pham Thanh, Duy %A Claire Jenkins %A Weill, François-Xavier %A Benjamin P Howden %A Mary Valcanis %A De Lappe, Niall %A Martin Cormican %A Sonam Wangchuk %A Ladaporn Bodhidatta %A Carl J Mason %A Nguyen, To Nguyen Thi %A Ha Thanh, Tuyen %A Phat Vinh Voong %A Duong, Vu Thuy %A Phu Huong Lan Nguyen %A Paul Turner %A Ryan Wick %A Pieter-Jan Ceyssens %A Guy Thwaites %A Kathryn E Holt %A Nicholas R Thomson %A Maia A Rabaa %A Stephen Baker %K Antimicrobial resistance %K Evolution %K fluoroquinolone %K Genomics %K Shigella sonnei %X

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.

%B Nat Commun %V 10 %8 2019 10 23 %G eng %N 1 %R 10.1038/s41467-019-12823-0