South Asia as a reservoir for the global spread of ciprofloxacin resistantShigella sonnei

AbstractBackgroundAntimicrobial resistance is a major issue in theShigellae, particularly as a specific multidrug resistant (MDR) lineage ofShigella sonnei(lineage III) is becoming globally dominant. Ciprofloxacin is a recommended treatment forShigellainfections. However, ciprofloxacin resistantS. sonneiare being increasingly isolated in Asia, and sporadically reported on other continents.Methods and FindingsHypothesising that Asia is the hub for the recent international spread of ciprofloxacin resistantS. sonnei, we performed whole genome sequencing on a collection of contemporaneous ciprofloxacin resistantS. sonneiisolated 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 resistantS. sonneiformed a single clade within a Central Asian expansion of Lineage III. Further, our data show that resistance to ciprofloxacin withinS. sonneican be globally attributed to a single clonal emergence event, encompassing sequentialgyrA-S83L,parC-S80I andgyrA-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.ConclusionsThis study shows that a single clone, which is widespread in South Asia, is driving the current intercontinental surge of ciprofloxacin resistantS. sonneiand 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 resistantS. sonnei, and provides a tractable model for studying how antimicrobial resistant Gram-negative community acquired pathogens spread globally.