Journal Article

South Asia as a Reservoir for the Global Spread of Ciprofloxacin-Resistant Shigella sonnei: A Cross-Sectional Study

Phu Huong Lan, Nguyen, De Lappe, Niall, Ha Thanh, Tuyen, Turner, Paul, Valcanis, Mary, Howden, Benjamin P., Nguyen Thi Nguyen, To, Pham Thanh, Duy, Cormican, Martin, Bodhidatta, Ladaporn, Thompson, Corinne N., Holt, Kathryn E., Mason, Carl J., Voong Vinh, Phat, Sar, Poda, Wangchuk, Sonam, Thwaites, Guy, Rabaa, Maia A., Thomson, Nicholas R., Vu Thuy, Duong, Chung The, Hao, Baker, Stephen

2016

Overview

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. We hypothesized that Asia is a primary hub for the recent international spread of ciprofloxacin-resistant S. sonnei. We performed whole-genome sequencing on a collection of 60 contemporaneous ciprofloxacin-resistant S. sonnei isolated in four countries within Asia (Vietnam, n = 11; Bhutan, n = 12; Thailand, n = 1; Cambodia, n = 1) and two outside of Asia (Australia, n = 19; Ireland, n = 16). 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. Furthermore, our data show that resistance to ciprofloxacin within S. sonnei may 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 United States and Europe. Our analysis was limited by the number of S. sonnei sequences available from diverse geographical areas and time periods, and we cannot discount the potential existence of other unsampled reservoir populations of antimicrobial-resistant S. sonnei. This study suggests that a single clone, which is widespread in South Asia, is likely 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 pathogens, with S. sonnei acting as a tractable model for studying how antimicrobial-resistant Gram-negative bacteria spread globally.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Anti-Bacterial Agents - therapeutic use / Antimicrobial agents / Australia - epidemiology / Bacteria / Bhutan - epidemiology / Biology and Life Sciences / Cambodia - epidemiology / Care and treatment / Child, Preschool / Ciprofloxacin / Ciprofloxacin - therapeutic use / Cloning / Computer and Information Sciences / Cross-Sectional Studies / Diarrhea / Drug resistance / Drug Resistance, Bacterial - genetics / Drug Resistance, Multiple, Bacterial - genetics / Dysentery, Bacillary - drug therapy / Dysentery, Bacillary - epidemiology / Dysentery, Bacillary - microbiology / Earth Sciences / Ecology and Environmental Sciences / Epidemiology / Exports / Genome, Bacterial - genetics / Genomes / Gram-negative bacteria / Humans / Infections / Ireland - epidemiology / Medicine and Health Sciences / Mortality / Mutation / People and Places / Phylogeny / Public health / Research and Analysis Methods / Shigella sonnei / Shigella sonnei - drug effects / Shigella sonnei - genetics / Shigellosis / Studies / Thailand - epidemiology / Vietnam - epidemiology