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Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei

Author

Listed:
  • Hao Chung The

    (Oxford University Clinical Research Unit)

  • Christine Boinett

    (Oxford University Clinical Research Unit
    Oxford University)

  • Duy Pham Thanh

    (Oxford University Clinical Research Unit)

  • Claire Jenkins

    (Public Health England)

  • Francois-Xavier Weill

    (Unité des Bactéries Pathogènes Entériques)

  • Benjamin P. Howden

    (The University of Melbourne)

  • Mary Valcanis

    (The University of Melbourne)

  • Niall De Lappe

    (University Hospital Galway)

  • Martin Cormican

    (National University of Ireland Galway)

  • Sonam Wangchuk

    (Royal Government of Bhutan)

  • Ladaporn Bodhidatta

    (Armed Forces Research Institute of Medical Sciences)

  • Carl J. Mason

    (Armed Forces Research Institute of Medical Sciences)

  • To Nguyen Thi Nguyen

    (Oxford University Clinical Research Unit)

  • Tuyen Ha Thanh

    (Oxford University Clinical Research Unit)

  • Vinh Phat Voong

    (Oxford University Clinical Research Unit)

  • Vu Thuy Duong

    (Oxford University Clinical Research Unit)

  • Phu Huong Lan Nguyen

    (Oxford University Clinical Research Unit
    The Hospital for Tropical Diseases)

  • Paul Turner

    (Oxford University
    Angkor Hospital for Children)

  • Ryan Wick

    (Monash University)

  • Pieter-Jan Ceyssens

    (Unit Bacterial Diseases, Sciensano)

  • Guy Thwaites

    (Oxford University Clinical Research Unit
    Oxford University)

  • Kathryn E. Holt

    (Monash University
    London School of Hygiene and Tropical Medicine)

  • Nicholas R. Thomson

    (London School of Hygiene and Tropical Medicine
    The Wellcome Trust Sanger Institute, Hinxton)

  • Maia A. Rabaa

    (Oxford University Clinical Research Unit
    Oxford University)

  • Stephen Baker

    (Oxford University Clinical Research Unit
    Oxford University
    Cambridge Institute of Therapeutic Immunology and Infectious Disease, The Department of Medicine, University of Cambridge)

Abstract

Shigella sonnei increasingly dominates the international epidemiological landscape of shigellosis. Treatment options for S. sonnei are dwindling due to resistance to several key antimicrobials, including the fluoroquinolones. Here we analyse nearly 400 S. sonnei whole genome sequences from both endemic and non-endemic regions to delineate the evolutionary history of the recently emergent fluoroquinolone-resistant S. sonnei. We reaffirm that extant resistant organisms belong to a single clonal expansion event. Our results indicate that sequential accumulation of defining mutations (gyrA-S83L, parC-S80I, and gyrA-D87G) led to the emergence of the fluoroquinolone-resistant S. sonnei population around 2007 in South Asia. This clone was then transmitted globally, resulting in establishments in Southeast Asia and Europe. Mutation analysis suggests that the clone became dominant through enhanced adaptation to oxidative stress. Experimental evolution reveals that under fluoroquinolone exposure in vitro, resistant S. sonnei develops further intolerance to the antimicrobial while the susceptible counterpart fails to attain complete resistance.

Suggested Citation

  • Hao Chung The & Christine Boinett & Duy Pham Thanh & Claire Jenkins & Francois-Xavier Weill & Benjamin P. Howden & Mary Valcanis & Niall De Lappe & Martin Cormican & Sonam Wangchuk & Ladaporn Bodhidat, 2019. "Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12823-0
    DOI: 10.1038/s41467-019-12823-0
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