Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei

Hao Chung The (1) , Christine Boinett (1) , Duy Pham Thanh (1) , Claire R Jenkins (2) , François-Xavier Weill (3) , Benjamin Howden (4) , Mary Valcanis (4) , Niall de Lappe (5) , Martin Cormican (6) , Sonam Wangchuk (7) , Ladaporn Bodhidatta (8) , Carl J Mason (8) , To Nguyen Thi Nguyen (1) , Tuyen Ha Thanh (1) , Vinh Phat Voong (1) , Vu Thuy Duong (1) , Phu Huong Lan Nguyen (9) , Paul Turner (10, 11) , Ryan Wick (12) , Pieter-Jan Ceyssens (13) , Guy Thwaites (10, 1) , Kathryn E Holt (12, 14) , Nicholas R Thomson (15, 14) , Maia A Rabaa (1, 10) , Stephen Baker (1, 10, 16)

1 OUCRU - Oxford University Clinical Research Unit [Ho Chi Minh City]
2 Public Health England [London]
3 CNR-ESS - Centre National de Référence - National Reference Center Escherichia coli, Shigella et Salmonella
4 The Peter Doherty Institute for Infection and Immunity [Melbourne]
5 University Hospital Galway
6 NUI Galway - National University of Ireland [Galway]
7 Ministry of Health [Bhoutan]
8 AFRIMS - Armed Forces Research Institute of Medical Sciences [Bangkok]
9 Hospital for Tropical Diseases
10 Centre for Tropical Medicine and Global Health [Oxford, UK]
11 AHC - Angkor Hospital for Children
12 Monash University [Melbourne]
13 Sciensano [Bruxelles]
14 LSHTM - London School of Hygiene and Tropical Medicine
15 The Wellcome Trust Sanger Institute [Cambridge]
16 CAM - University of Cambridge [UK]

Shigella sonnei increasingly dominates the international epidemiological landscape of shi-gellosis. 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.

Domains: Bacteriology

Hao Chung The, Christine Boinett, Duy Pham Thanh, Claire R Jenkins, François-Xavier Weill, et al.. Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei. Nature Communications, 2019, 10 (1), pp.4828. ⟨10.1038/s41467-019-12823-0⟩. ⟨pasteur-02481816⟩