The evolutionary history of Shigella flexneri serotype 6 in Asia
Abstract
Shigella flexneri serotype 6 is an understudied cause of diarrhoeal diseases in developing countries, and has been proposed as one of the major targets for vaccine development against shigellosis. Despite being named as S. flexneri , Shigella flexneri serotype 6 is phylogenetically distinct from other S. flexneri serotypes and more closely related to S. boydii . This unique phylogenetic relationship and its low sampling frequency have hampered genomic research on this pathogen. Herein, by utilizing whole genome sequencing (WGS) and analyses of Shigella flexneri serotype 6 collected from epidemiological studies (1987–2013) in four Asian countries, we revealed its population structure and evolutionary history in the region. Phylogenetic analyses supported the delineation of Asian Shigella flexneri serotype 6 into two phylogenetic groups (PG-1 and −2). Notably, temporal phylogenetic approaches showed that extant Asian S. flexneri serotype 6 could be traced back to an inferred common ancestor arising in the 18th century. The dominant lineage PG-1 likely emerged in the 1970s, which coincided with the times to most recent common ancestors (tMRCAs) inferred from other major Southeast Asian S. flexneri serotypes. Similar to other S. flexneri serotypes in the same period in Asia, genomic analyses showed that resistance to first-generation antimicrobials was widespread, while resistance to more recent first-line antimicrobials was rare. These data also showed a number of gene inactivation and gene loss events, particularly on genes related to metabolism and synthesis of cellular appendages, emphasizing the continuing role of reductive evolution in the adaptation of the pathogen to an intracellular lifestyle. Together, our findings reveal insights into the genomic evolution of the understudied Shigella flexneri serotype 6, providing a new piece in the puzzle of Shigella epidemiology and evolution.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 24, 2021
- Source ID
- 10.1099/mgen.0.000736
Entities
People
- Duy Thanh Pham
- Guy E. Thwaites
- Hao Chung The
- Ladaporn Bodhidatta
- Maia A. Rabaa
- Nicholas Thomson
- Paul Turner
- Phat Voong Vinh
- Sonam Wangchuk
- Stephen Baker
- T. Si-Nguyen
- Tuyen Ha Thanh
Organizations
- Angkor Hospital for Children
- Armed Forces Research Institute of Medical Sciences
- London School of Hygiene & Tropical Medicine
- University of Cambridge
- University of Groningen
- University of Oxford
- Wellcome
- Wellcome Sanger Institute