bioRxiv Science⌕ Search

bioRxiv · 10.1101/798835

Persistent transmission of shigellosis in England is associated with a recently emerged multi-drug resistant strain of Shigella sonnei

Abstract

BackgroundWhole genome sequencing has enhanced surveillance and facilitated detailed monitoring of transmission of Shigella species in England.\n\nMethodsWe undertook an epidemiological and phylogenetic analysis of isolates from all cases of shigellosis referred to Public Health England between 2015 to 2018 to explore recent strain characteristics and transmission dynamics of Shigella species.\n\nResultsOf the 4950 confirmed cases of shigellosis identified during this period, the highest proportion of isolates were S. sonnei (54.4%), followed by S. flexneri (39.2%), S. boydii (4.1%) and S. dysenteriae (2.2%). Most cases were adults (82.9%) and male (59.5%), and 34.9% cases reported recent travel outside the UK. Throughout the study period diagnoses of S. flexneri and S. sonnei were most common in men with no history of recent travel abroad. Species prevalence was not static with cases of S. flexneri in men decreasing from 2015-2016, and the number of cases of S. sonnei increasing from 2017. Phylogenetic analysis showed this recent increase in S. sonnei was attributed to a novel clade exhibiting resistance to ciprofloxacin and azithromycin, which had emerged from a Central Asia sub-lineage.\n\nConclusionsDespite changes in species prevalence, Shigella diagnoses in England are persistently the most common in adult males without reported travel history, consistent with sexual transmission amongst men who have sex with men. The trend in increasing ciprofloxacin resistance, in addition to plasmid-mediated azithromycin resistance, in S. sonnei is of significant public health concern with respect to transmission of multi-drug resistant gastrointestinal pathogens and the risk of treatment failures.\n\nSummaryShigella diagnoses in England are most prevalent amongst men who have sex with men. S. sonnei exhibiting resistance to both azithromycin and ciprofloxacin has replaced azithromycin-resistant S. flexneri as the most commonly isolated species in this setting.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Jenkins, C., Bardsley, M., Mitchell, H. D., Mikhail, A. F. W., Baker, K. S., Foster, K., Hughes, G., Dallman, T. J.. 2019-10-09. Persistent transmission of shigellosis in England is associated with a recently emerged multi-drug resistant strain of Shigella sonnei. https://doi.org/10.1101/798835

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Long-read DNA sequencing reveals global hypomethylation and focal hypermethylation in SDHx-deficient pheochromocytoma and paraganglioma

Pheochromocytomas and paragangliomas (PPGL) are highly heritable neuroendocrine tumors of the autonomic ganglia. Genomic DNA in most cancer cells is hypomethylated. However, DNA in PPGLs secondary to mutations in succinate dehydrogenase complex (SDHx) genes is reportedly hypermethylated due to succinate-mediated inhibition of DNA demethylases. We used nanopore long-read sequencing to characterize the methylome of tumor and white blood cell DNA from SDHx and non-SDHx PPGL patients, alongside normal adrenal medulla. We find that both SDHx and non-SDHx PPGLs are globally hypomethylated, particularly at centromeres. In normal adrenal medulla, CpG islands marked by H3K4 methylation are hypomethylated, whereas CpG islands lacking H3K4 methylation are hypermethylated. In SDHx-related PPGL, some H3K4me-marked CpG islands are hypermethylated, but most are not. We propose that DNA methylation in SDHx-related PPGL reflects the global hypomethylation generally observed in tumors, partly offset by succinate-mediated inhibition of TET DNA demethylases. Opposing effects of succinate may alter the balance between DNA methylation (indirect inhibition of the DNMT3A/B DNA methylases via inhibition of H3K4me demethylases) and DNA demethylation (inhibition of TET DNA demethylases) at active CpG islands.

genomics↗

High piRNA abundance is a hallmark of evolutionarily persistent piRNA-producing loci.

PIWI-interacting RNAs (piRNAs) silence transposons in the germline, and the loci that produce them diverge rapidly between species. Yet, some loci retain both their genomic location and their piRNA production across large evolutionary distances, and the basis for this conservation is unclear. To identify the features that distinguish these persistent loci, we compared piRNA production at orthologous loci in three closely related mouse species, contrasting loci that produce piRNAs in all three species with those that do so in only one. Transposon content and UTR features, often linked to piRNA production, did not distinguish the two groups. Transcription extending beyond gene ends (readthrough) was more frequent at conserved loci, but did not explain conservation once the amount of piRNAs produced was taken into account. Instead, we found that the conserved loci are those that produce the most piRNAs. The same association holds true in human and two other primate species. We speculate that most piRNAs expressed in testis are tolerated molecular noise, and that only the highly expressed minority are likely to be functional.

genomics↗

Epigenome-informed Polymer Modeling Reveals Chromosome Folding Landscapes across Distinct Genetic and Epigenetic Contexts

Three-dimensional (3D) genome organization is critical for gene regulation, enabling long-range interactions between genes and distal regulatory elements. Genomic structural variations and epigenetic differences can perturb this organization, contributing to phenotypic variation and tissue-specific gene regulation. Prior studies have assessed the impact of these genetic and epigenetic changes on 3D genome folding, primarily using population-averaged features such as topologically associating domains and loops. However, growing evidence from single-cell and live-imaging studies indicates that chromosomes are highly dynamic and exist as heterogeneous ensembles of conformations. Here, we applied an epigenetic-state-informed polymer modeling framework to generate chromosomal conformational ensembles directly from cell- and tissue-specific epigenomic data. The resulting ensembles reproduced experimental Hi-C maps across cell lines and tissue types. Comparison of these conformational ensembles revealed that, although polymer dynamics were conserved across cell lines, their folding landscapes diverged. These differences arose primarily from cell-line-specific chromatin-state interaction networks and were concentrated in rare, long-lived contacts. Furthermore, modeling a TAD-boundary-disrupting deletion without re-optimizing the model parameters indicated a shift in the chromatin conformational ensemble from predominantly insulated to predominantly fused states. The modeled deletion also selectively strengthened active chromatin contacts and differentially disrupted enhancer contacts involving neighboring genes. Finally, comparison of two tissue types from the same donor revealed epigenetically driven rewiring of chromatin-state interaction networks. These findings establish chromosomal conformational ensembles as a sensitive readout of genome reorganization across distinct genetic and epigenetic contexts.

genomics↗