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

Hao Chung The, Maia A. Rabaa, Duy Pham Thanh, Niall De Lappe, Martin Cormican, Mary Valcanis, Benjamin P. Howden, Sonam Wangchuk, Ladaporn Bodhidatta, Carl Jeffries Mason, To Nguyen Nguyen Thi, Duong Vu Thuy, Corinne N. Thompson, Nguyen Phu Huong Lan, Phat Voong Vinh, Tuyen Ha Thanh, Paul Turner, Poda Sar, Guy Thwaites, Nicholas R. Thompson, Kathryn E. Holt, Stephen Baker
doi: https://doi.org/10.1101/041327
Hao Chung The
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
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Maia A. Rabaa
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
2Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom
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Duy Pham Thanh
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
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Niall De Lappe
3National Salmonella, Shigella and Listeria monocytogenes Reference Laboratory, University Hospital Galway, Galway, Ireland
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Martin Cormican
4School of Medicine, National University of Ireland Galway, Galway, Ireland
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Mary Valcanis
5Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology,Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Australia
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Benjamin P. Howden
5Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology,Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Australia
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Sonam Wangchuk
6Public Health Laboratory, Department of Public Health, Ministry of Health, Royal Government of Bhutan,Thimphu, Bhutan
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Ladaporn Bodhidatta
7Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand
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Carl Jeffries Mason
7Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand
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To Nguyen Nguyen Thi
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
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Duong Vu Thuy
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
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Corinne N. Thompson
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
2Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom
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Nguyen Phu Huong Lan
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
8The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
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Phat Voong Vinh
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
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Tuyen Ha Thanh
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
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Paul Turner
2Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom
9Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
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Poda Sar
9Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
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Guy Thwaites
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
2Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom
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Nicholas R. Thompson
10The London School of Hygiene and Tropical Medicine, London, United Kingdom
11The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom
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Kathryn E. Holt
12Centre for Systems Genomics, The University of Melbourne, Australia
13Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute,University of Melbourne, Australia
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Stephen Baker
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University ClinicalResearch Unit, Ho Chi Minh City, Vietnam
2Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom
11The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom
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  • For correspondence: sbaker@oucru.org
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Abstract

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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 25, 2016.
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South Asia as a reservoir for the global spread of ciprofloxacin resistant Shigella sonnei
Hao Chung The, Maia A. Rabaa, Duy Pham Thanh, Niall De Lappe, Martin Cormican, Mary Valcanis, Benjamin P. Howden, Sonam Wangchuk, Ladaporn Bodhidatta, Carl Jeffries Mason, To Nguyen Nguyen Thi, Duong Vu Thuy, Corinne N. Thompson, Nguyen Phu Huong Lan, Phat Voong Vinh, Tuyen Ha Thanh, Paul Turner, Poda Sar, Guy Thwaites, Nicholas R. Thompson, Kathryn E. Holt, Stephen Baker
bioRxiv 041327; doi: https://doi.org/10.1101/041327
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South Asia as a reservoir for the global spread of ciprofloxacin resistant Shigella sonnei
Hao Chung The, Maia A. Rabaa, Duy Pham Thanh, Niall De Lappe, Martin Cormican, Mary Valcanis, Benjamin P. Howden, Sonam Wangchuk, Ladaporn Bodhidatta, Carl Jeffries Mason, To Nguyen Nguyen Thi, Duong Vu Thuy, Corinne N. Thompson, Nguyen Phu Huong Lan, Phat Voong Vinh, Tuyen Ha Thanh, Paul Turner, Poda Sar, Guy Thwaites, Nicholas R. Thompson, Kathryn E. Holt, Stephen Baker
bioRxiv 041327; doi: https://doi.org/10.1101/041327

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