Evolutionary histories and antimicrobial resistance inShigella flexneri and Shigella sonnei in Southeast Asia

Abstract

Conventional disease surveillance for shigellosis in developing country settingsrelies on serotyping and low-resolution molecular typing, which fails to contextualise the evolutionary history of the genus. Here, we interrogated a collection of 1,804 Shigella whole genome sequences from organisms isolated in four continental Southeast Asian countries (Thailand, Vietnam, Laos, and Cambodia) over three decades to characterise the evolution of both S. flexneri and S. sonnei. We show that S. sonnei and each major S. flexneri serotype are comprised of genetically diverse populations, the majority of which were likely introduced into Southeast Asia in the 1970s-1990s. Intranational and regional dissemination allowed widespread propagation of both species across the region. Our data indicate that the epidemiology of S. sonnei and the major S. flexneri serotypes were characterised by frequent clonal replacement events, coinciding with changing susceptibility patterns against contemporaneous antimicrobials. We conclude that adaptation to antimicrobial pressure was pivotal to the recent evolutionary trajectory of Shigella in Southeast Asia.

Characterization of Shigella flexneri in northern Vietnam in 2012–2016

“…Another feature discriminating between Lin-3.1 and Lin-3.2 is quinolone resistance. Quinolone resistance emerged in the mid-1990s both in Lin-3.1 and in Lin-3.2, and became prevalent in the mid-2010s in Lin-3.1 but not in Lin-3.2 [8]. These features corresponded to those of the sub-lineages found in this study.…”

“…No other types of gyrA mutation were found in this study. A recent study identified two sub-lineages in PG3, Lin-3.1 and Lin-3.2 [8]. The resistance gene for trimethoprim is one of the key features for each Lin; Lin-3.2 was associated with dfrA1 while Lin-3.1 independently acquired a plasmid-borne dfrA14.…”

“…S. sonnei has been increasing in prevalence and is replacing S. flexneri, even in developing countries, including in Southeast Asia [3,6]. In Vietnam, this species replacement is significant in the southern region [7,8]. However, shigellosis outbreaks due to S. flexneri continue to occur, and information on the genomic characterization remains limited.…”

Molecular Characterization of Multidrug-Resistant Shigella flexneri

“…It emphasized the geographic variation in antibiotic resistance, with factors like customs, climate, and economies influencing antimicrobial susceptibility [23]. Furthermore, a study in China identified a significant shift in trimethoprim resistance in S. flexneri over time, with certain variants linked to resistance and plasmid-borne antimicrobial resistance (AMR) gene clusters observed [24].…”

Shigella sonnei utilises colicins during inter-bacterial competition

“…It remains a major cause of infant morbidity and mortality for children under the age of five, especially in resource-limited nations [1]. In resource-rich nations, Shigella has become an emerging pathogen of concern due to extensive and expanding resistance to multiple classes of antimicrobial drugs [2][3][4][5][6][7][8][9]. Shigella is spread via the faecal-oral route, most commonly through contaminated food and water sources but also via fomites.…”