RT Journal Article SR Electronic T1 South Asia as a reservoir for the global spread of ciprofloxacin resistant Shigella sonnei JF bioRxiv FD Cold Spring Harbor Laboratory SP 041327 DO 10.1101/041327 A1 Hao Chung The A1 Maia A. Rabaa A1 Duy Pham Thanh A1 Niall De Lappe A1 Martin Cormican A1 Mary Valcanis A1 Benjamin P. Howden A1 Sonam Wangchuk A1 Ladaporn Bodhidatta A1 Carl Jeffries Mason A1 To Nguyen Nguyen Thi A1 Duong Vu Thuy A1 Corinne N. Thompson A1 Nguyen Phu Huong Lan A1 Phat Voong Vinh A1 Tuyen Ha Thanh A1 Paul Turner A1 Poda Sar A1 Guy Thwaites A1 Nicholas R. Thompson A1 Kathryn E. Holt A1 Stephen Baker YR 2016 UL http://biorxiv.org/content/early/2016/02/25/041327.abstract AB Background Antimicrobial resistance is a major issue in the Shigellae, particularly as a specific multidrug resistant (MDR) lineage of Shigella sonnei (lineage III) is becoming globally dominant. Ciprofloxacin is a recommended treatment for Shigella infections. However, ciprofloxacin resistant S. sonnei are being increasingly isolated in Asia, and sporadically reported on other continents.Methods and Findings Hypothesising that Asia is the hub for the recent international spread of ciprofloxacin resistant S. sonnei, we performed whole genome sequencing on a collection of contemporaneous ciprofloxacin resistant S. sonnei isolated in six countries from within and outside of Asia. We reconstructed the recent evolutionary history of these organisms and combined these data with their geographical location of isolation. Placing these sequences into a global phylogeny we found that all ciprofloxacin resistant S. sonnei formed a single clade within a Central Asian expansion of Lineage III. Further, our data show that resistance to ciprofloxacin within S. sonnei can be globally attributed to a single clonal emergence event, encompassing sequential gyrA-S83L, parC-S80I and gyrA-D87G mutations. Geographical data predict that South Asia is the likely primary source of these organisms, which are being regularly exported across Asia and intercontinentally into Australia, the USA and Europe.Conclusions This study shows that a single clone, which is widespread in South Asia, is driving the current intercontinental surge of ciprofloxacin resistant S. sonnei and is capable of establishing endemic transmission in new locations. Despite being limited in geographical scope, our work has major implications for understanding the international transfer of antimicrobial resistant S. sonnei, and provides a tractable model for studying how antimicrobial resistant Gram-negative community acquired pathogens spread globally.