South Asia as a reservoir for the global spread of ciprofloxacin resistant Shigella sonnei
Chung The H., Rabaa M., Pham Thanh D., De Lappe N., Cormican M., Howden B., Wangchuk S., Bodhidatta L., Jeffries C., Nguyen Thi Nguyen T., Vu Thuy D., Thompson C., Phu Huong Lan N., Voong Vinh P., Ha Thanh T., Turner P., Sar P., Thwaites G., Thompson N., Holt K., Baker S.
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.