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

Citation: Chung The H, Rabaa MA, Pham Thanh D, De Lappe N, Cormican M, Valcanis M, et al. (2016) South Asia as a Reservoir for the Global Spread of Ciprofloxacin-Resistant Shigella sonnei: A Cross-Sectional Study. PLoS Med 13(8): e1002055. doi:10.1371/journal.pmed.1002055
Published: August 2, 2016

Abstract
ciprofloxacin-zwitterion-from-xtal-3d-ballsBackground: 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.
Methods and Findings: 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.
Conclusions: 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.

Author Summary

Why Was This Study Done?

  • Antimicrobial resistance is a major issue in Shigella, and ciprofloxacin is a recommended treatment for Shigella infections.
  • Ciprofloxacin-resistant Shigella sonnei are being increasingly isolated globally.

What Did the Researchers Do and Find?

  • We performed genome sequencing on 60 ciprofloxacin-resistant S. sonnei isolated in six countries within and outside of Asia.
  • Placing these genome sequences in context with other strains, we found that all ciprofloxacin-resistant S. sonnei formed a single clade, with South Asia as the likely primary source of these organisms.
  • These organisms are also being regularly exported across Asia and intercontinentally into Australia, the United States, and Europe.
  • The number of S. sonnei sequences available from other locations limited our analysis.

What Do These Findings Mean?

  • Our work suggests that a single clone, which is widespread in South Asia, is driving the current global surge of ciprofloxacin-resistant S. sonnei.
  • We argue that S. sonnei acts as a tractable model for studying how antimicrobial-resistant, Gram-negative bacteria spread globally.

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