title: Introduction and establishment of fluoroquinolone-resistantShigella sonneiinto Bhutan.
abstract: Shigella sonneiis a major contributor to the global burden of diarrhoeal disease, generally associated with dysenteric diarrhoea in developed countries but also emerging in developing countries. The reason for the recent success ofS. sonneiis unknown, but is likely catalysed by its ability to acquire resistance against multiple antimicrobials. Between 2011 and 2013,S. sonneiexhibiting resistance to fluoroquinolones, the first-line treatment recommended for shigellosis, emerged in Bhutan. Aiming to reconstruct the introduction and establishment of fluoroquinolone-resistantS. sonneipopulations in Bhutan, we performed whole-genome sequencing on 71S. sonneisamples isolated in Bhutan between 2011 and 2013.We found that these strains represented an expansion of a clade within the previously described lineage III, found specifically in Central Asia. Temporal phylogenetic reconstruction demonstrated that all of the sequenced BhutaneseS. sonneidiverged from a single ancestor that was introduced into Bhutan around 2006. Our data additionally predicted that fluoroquinolone resistance, conferred by mutations ingyrAandparC, arose prior to the introduction of the founder strain into Bhutan. Once established in Bhutan, theseS. sonneihad access to a broad gene pool, as indicated by the acquisition of extended-spectrum β-lactamase-encoding plasmids and genes encoding type IV pili. The data presented here outline a model for the introduction and maintenance of fluoroquinolone-resistantS. sonneiin a new setting. Given the current circulation of fluoroquinolone-resistantS. sonneiin Asia, we speculate that this pattern of introduction is being recapitulated across the region and beyond.
authors.affiliation: The Hospital for Tropical Diseases, OUCRU, Ho Chi Minh City, Vietnam.
authors.forename: Hao
authors.initials: H
authors.lastname: Chung The
authors.affiliation: The Hospital for Tropical Diseases, OUCRU, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Oxford University, Oxford, UK.
authors.forename: Maia A
authors.initials: MA
authors.lastname: Rabaa
authors.affiliation: The Hospital for Tropical Diseases, OUCRU, Ho Chi Minh City, Vietnam.
authors.forename: Duy Pham
authors.initials: DP
authors.lastname: Thanh
authors.affiliation: Department of Enteric Diseases, AFRIMS, Bangkok, Thailand.
authors.forename: Sirigade
authors.initials: S
authors.lastname: Ruekit
authors.affiliation: Public Health Laboratory, Department of Public Health, Ministry of Health, Royal Government of Bhutan, Thimphu, Bhutan.
authors.forename: Sonam
authors.initials: S
authors.lastname: Wangchuk
authors.affiliation: Public Health Laboratory, Department of Public Health, Ministry of Health, Royal Government of Bhutan, Thimphu, Bhutan.
authors.forename: Tshering
authors.initials: T
authors.lastname: Dorji
authors.affiliation: Department of Pediatrics, Jigme Dorji Wangchuk Referral Hospital, Kawa Jangsa, Thimphu, Bhutan.
authors.forename: Kinzang Pem
authors.initials: KP
authors.lastname: Tshering
authors.affiliation: The Hospital for Tropical Diseases, OUCRU, Ho Chi Minh City, Vietnam.
authors.forename: To Nguyen Thi
authors.initials: TNT
authors.lastname: Nguyen
authors.affiliation: The Hospital for Tropical Diseases, OUCRU, Ho Chi Minh City, Vietnam.
authors.forename: Phat Voong
authors.initials: PV
authors.lastname: Vinh
authors.affiliation: The Hospital for Tropical Diseases, OUCRU, Ho Chi Minh City, Vietnam.
authors.forename: Tuyen Ha
authors.initials: TH
authors.lastname: Thanh
authors.affiliation: The Hospital for Tropical Diseases, OUCRU, Ho Chi Minh City, Vietnam.
authors.forename: Chau Nguyen Ngoc
authors.initials: CNN
authors.lastname: Minh
authors.affiliation: Centre for Tropical Medicine, Oxford University, Oxford, UK.|Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Paul
authors.initials: P
authors.lastname: Turner
authors.affiliation: Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Poda
authors.initials: P
authors.lastname: Sar
authors.affiliation: The Hospital for Tropical Diseases, OUCRU, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Oxford University, Oxford, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Thwaites
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.|The London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.affiliation: Department of Enteric Diseases, AFRIMS, Bangkok, Thailand.
authors.forename: Ladaporn
authors.initials: L
authors.lastname: Bodhidatta
authors.affiliation: Department of Enteric Diseases, AFRIMS, Bangkok, Thailand.
authors.forename: Carl
authors.initials: C
authors.lastname: Jeffries Mason
authors.affiliation: The Hospital for Tropical Diseases, OUCRU, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, Oxford University, Oxford, UK.|The London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
keywords: Bhutan; Shigella sonnei; fluoroquinolone; resistance