Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei

• DOI: 10.1038/s41467-019-12823-0
• Publication Date: 2019-10-23T11:06:43Z
• Authors: Hao Chung The; Christine Boinett; Duy Pham Thanh; Claire Jenkins; Francois-Xavier W...; 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; Stephen Baker
• Keywords: DNA Topoisomerase IV; 0301 basic medicine; Science; 610; /45/22; Shigella sonnei; /631/208/325/2482; /45/23; Polymorphism, Single Nucleotide; Article; Evolution, Molecular; 03 medical and health sciences; Ciprofloxacin; Drug Resistance, Bacterial; Asia, Western; Humans; Asia, Southeastern; Phylogeny; Dysentery, Bacillary; Molecular Epidemiology; /45; /631/326/421; Q; article; Bayes Theorem; [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology; Anti-Bacterial Agents; 3. Good health; Europe; DNA Gyrase; /692/699/255/1318; /631/326/22/1434; Mutation; Directed Molecular Evolution; Genome, Bacterial; Fluoroquinolones

AbstractShigella sonneiincreasingly dominates the international epidemiological landscape of shigellosis. Treatment options forS. sonneiare dwindling due to resistance to several key antimicrobials, including the fluoroquinolones. Here we analyse nearly 400 S. sonneiwhole genome sequences from both endemic and non-endemic regions to delineate the evolutionary history of the recently emergent fluoroquinolone-resistantS. 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, andgyrA-D87G) led to the emergence of the fluoroquinolone-resistantS. sonneipopulation 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, resistantS. sonneidevelops further intolerance to the antimicrobial while the susceptible counterpart fails to attain complete resistance.