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 CeyssensGuy Thwaites, Kathryn E. Holt, Nicholas R. Thomson, Maia A. Rabaa, Stephen Baker

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Article number4828
Number of pages13
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Cite this

Chung The, H., Boinett, C., Pham Thanh, D., Jenkins, C., Weill, F. X., Howden, B. P., Valcanis, M., De Lappe, N., Cormican, M., Wangchuk, S., Bodhidatta, L., Mason, C. J., Nguyen, T. N. T., Ha Thanh, T., Voong, V. P., Duong, V. T., Nguyen, P. H. L., Turner, P., Wick, R., ... Baker, S. (2019). Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei. Nature Communications, 10(1), [4828]. https://doi.org/10.1038/s41467-019-12823-0