Informing shigellosis prevention and control through pathogen genomics

Rj, Bengtsson; Simpkin, Adam J; Cv, Pulford; Low, Ross; Da, Rasko; Rigden, Daniel J.; Hall, Neil; Em, Barry; Sm, Tennant; Baker, Kate S.

doi:10.1101/2021.06.09.447709

Cited by 2 publications

(2 citation statements)

References 84 publications

(94 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For S. sonnei, different sub-lineages have been identified [20][21][22] , however only one S. sonnei serotype exists (Figure S2G), which has comparable genetic diversity to individual serotypes of S. flexneri (e.g. S. flexneri 2a) 23,24 . Both representatives of the persistence ingroup and the persistence outgroup of S. sonnei persist in zebrafish in vivo.…”

Section: Shigella O-antigen Variants Circulating In the Msm Populatio...mentioning

confidence: 99%

Shigellaserotypes associated with carriage in humans establish persistent infection in zebrafish

Torraca

Brokatzky

Miles

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Shigella represents a paraphyletic group of human-adapted Escherichia coli lineages that converged towards the same enteropathogenic pathovar. In low-income countries, Shigella is typically transmitted by ingestion of contaminated water and food, while in high-income countries sexual transmission among men who have sex with men (MSM) is the dominant route of transmission. Although more than 40 different serotypes of Shigella have been reported globally, within the MSM community the majority of reported cases are attributed to three Shigella serotypes: the Shigella sonnei unique serotype (Ss) and the Shigella flexneri serotypes 2a and 3a. Here, using a zebrafish infection model, we demonstrate that Shigella can establish persistent infection in vivo. In this case, bacteria are not cleared by the host immune system and become tolerant to therapeutic doses of antibiotics. We show that persistence is dependent on the Shigella O-Antigen, a key constituent of the bacterial cell surface and determinant of serotype classification. Representative isolates of three Shigella serotypes associated with global dissemination and MSM transmission (S. sonnei Ss, S. flexneri 2a and 3a) all persist in zebrafish, while a serotype not associated with MSM transmission (S. flexneri 5a) does not. Strikingly, Shigella serotypes which establish persistent infection fail to promote macrophage cell death in vivo. We conclude that zebrafish can be a valuable platform to illuminate host and pathogen factors underlying the establishment of persistent infection with Shigella in humans.

show abstract

Section: Shigella O-antigen Variants Circulating In the Msm Populatio...mentioning

confidence: 99%

Shigellaserotypes associated with carriage in humans establish persistent infection in zebrafish

Torraca

Brokatzky

Miles

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The pINV encodes genes that facilitate several interactions with the host cell machinery enabling the bacterium to survive and replicate in the human host cells (Schroeder and Hilbi, 2008). Two species of Shigella, S. sonnei and S. flexneri, are responsible for the main burden of disease of Shigellosis globally (Bengtsson et al, 2022). These species may have different plasmids.…”

Section: Introductionmentioning

confidence: 99%

Tracking the horizontal transfer of plasmids inShigella sonneiandShigella flexneriusing phylogenetics

Müller

Duchêne

Williamson

et al. 2022

Preprint

View full text Add to dashboard Cite

There is an urgent need for novel methods to track the emergence and dissemination of antimicrobial resistance (AMR) mechanisms that give rise to multi- and extensively-drug resistant bacterial pathogens. AMR mechanisms are most commonly associated with AMR genes that are carried on mobile elements, such as plasmids. Plasmids may move between lineages of the same or different bacterial species and thus understanding when and where they were introduced into a population, as well as their persistence, is crucial to understanding the changing AMR dynamics in bacterial pathogens. Here we introduce an approach that allows us to reconstruct how plasmids move between bacterial lineages. To do so, we model the co-divergence of chromosomal and plasmid DNA in a Bayesian phylogenetic network approach using a joint coalescent and plasmid transfer process. We apply this new approach to a five year dataset ofShigella sonneiandShigella flexneriisolated in Melbourne, Australia, reconstructing how different plasmids move within and between these species. Specifically, we investigate the long term co-divergence of the virulence plasmid, the gain and loss of small plasmids, and the recent acquisition and dissemination of the multidrug resistant (MDR) plasmid moving betweenS. sonneiandS. flexnerilineages, through multiple introductions from sampled and also unsampled sources. This approach has applications to both emerging and known bacterial pathogens and improves our understanding of where AMR-carrying plasmids are introduced and maintained in bacterial pathogens of human health importance. Our novel approach is implemented in the widely used BEAST2 software.

show abstract

Informing shigellosis prevention and control through pathogen genomics

Cited by 2 publications

References 84 publications

Shigellaserotypes associated with carriage in humans establish persistent infection in zebrafish

Shigellaserotypes associated with carriage in humans establish persistent infection in zebrafish

Tracking the horizontal transfer of plasmids inShigella sonneiandShigella flexneriusing phylogenetics

Contact Info

Product

Resources

About