bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.10.16.343467

Salmonella Typhi acquires diverse plasmids from other Enterobacteriaceae to develop cephalosporin resistance

Jacob, J. J.·Pragasam, A. K.·Vasudevan, K.·Veeraraghavan, B.·Kang, G.·John, J.·Nagvekar, V.·Mutreja, A.
View original source ↗Export metadata ↓

Abstract

BackgroundRecent reports have established the emergence and dissemination of extensively drug resistant (XDR) H58 Salmonella Typhi clone in Pakistan. In India where typhoid fever is endemic, only sporadic cases of ceftriaxone resistant S. Typhi are reported. This study aimed at elucidating the phylogenetic evolutionary framework of ceftriaxone resistant S. Typhi isolates from India to predict their potential dissemination in endemic regions. MethodsFive ceftriaxone resistant S. Typhi isolates from three tertiary care hospitals in India were sequenced on an Ion Torrent Personal Genome Machine (PGM). A core genome single-nucleotide-polymorphism (SNP) based phylogeny of the isolates in comparison to the global collection of MDR and XDR S. Typhi isolates was built. Two of five isolates were additionally sequenced using Oxford Nanopore MinION to completely characterize the plasmid and understand its transmission dynamics within Enterobacteriaceae. ResultsComparative genomic analysis and detailed plasmid characterization indicate that while in Pakistan (4.3.1 lineage I) the XDR trait is associated with blaCTX-M-15 gene on IncY plasmid, in India (4.3.1 lineage II), the ceftriaxone resistance is due to short term adaptation of resistance plasmids such as IncX3 or IncN. ConclusionSince the bacterial acquisition of smaller resistance plasmids such as IncX3 or IncN from other Enterobacteriaceae can be much faster than the larger IncY plasmids, the rapid expansion of these genotypically novel XDR S. Typhi could potentially cause large outbreaks. Therefore, continuous monitoring of S. Typhi lineages carrying cephalosporin resistance on IncX3 or IncN plasmids is vital not just for India but globally. ImportanceGenomic analysis of cephalosporin resistant S. Typhi isolated from India indicates the potential of S. Typhi to develop cephalosporin resistance by acquiring diverse plasmids from other Enterobacteriaceae. We identified the occurrence of independent acquisition of drug-resistant plasmids such as IncX3 and IncN with genes encoding beta-lactamases in H58/4.3.1.2 lineage. A short term adaptation of drug-resistant plasmids in H58/4.3.1.2 lineage can be the reason for the sporadic cases cephalosporin resistant S. Typhi in India. However, the IncY plasmid acquired by isolates that belong to H58/4.3.1.1 lineage appeared to be well adapted as observed in XDR S. Typhi outbreak in Pakistan. Plasmid acquisition and maintenance of cephalosporin resistant S. Typhi appears to be specific to the phylogenetic lineage as lineages differ in compensating the initial cost imposed by the plasmid. The stable maintenance of these resistance plasmids without a fitness cost, are determinant in understanding the future spread of cephalosporin resistance in S. Typhi. Therefore, critical strategies in monitoring and control of cephalosporin resistant S. Typhi is needed to tackle further public health crisis.

Source connections

Explore related subjects

genomicsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Jacob, J. J., Pragasam, A. K., Vasudevan, K., Veeraraghavan, B., Kang, G., John, J., Nagvekar, V., Mutreja, A.. 2020-10-17. Salmonella Typhi acquires diverse plasmids from other Enterobacteriaceae to develop cephalosporin resistance. https://doi.org/10.1101/2020.10.16.343467

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

KEEP EXPLORING

Related preprints

bioRxiv2026

A hydrogen-producing mitochondrion in an anaerobic eukaryotrophic rhizarian

Diverse eukaryotes thrive under low oxygen conditions, in part through highly modified mitochondrion-related organelles (MROs) that use alternate metabolic pathways to support ATP production and cofactor recycling. Anaerobic lifestyles have evolved repeatedly across the eukaryotic tree of life, each providing an independent opportunity to understand how eukaryotes adapt to life in low oxygen conditions. Here, we use single-cell transcriptomics to reconstruct the MRO metabolism of PCE SSF, a benthic eukaryotrophic flagellate and the first cultivated representative of Novel Clade 12 (NC12; Rhizaria), an independently anaerobic rhizarian lineage. PCE SSF possesses an anaerobic hydrogen-producing mitochondrion capable of hydrogenosome-type substrate-level phosphorylation. It also retains a nearly complete but likely branched tricarboxylic acid pathway that lacks citrate synthase and malate dehydrogenase. The function of citrate synthase may instead be fulfilled by the typically cytosolic ATP citrate lyase, previously reported in this context only in the anaerobic cercozoan, Brevimastigomonas motovehiculus. Unlike B. motovehiculus, however, PCE SSF retains only Complex II and the NuoE/NuoF subunits of the electron transport chain and lacks a mitochondrial genome. Together, these features indicate an atypical and reduced mitochondrial metabolism, highlighting the diversity of evolutionary solutions to anaerobic energy metabolism in eukaryotes.

genomics↗
bioRxiv2026

A single-nucleus multi-omic atlas of gene regulation across 21 adult human tissues

Diverse human cell types establish specialized functions through lineage- and context-specific regulatory programs. Interpreting non-coding genetic risk requires integrated multi-omic reference maps that directly connect regulatory DNA to cellular expression across human tissues. Here we present a single-nucleus multi-omic atlas comprising 459,856 transcriptomic and chromatin accessibility profiles from 21 adult human tissues and four donors, including paired measurements from 160,688 nuclei. The atlas resolves nine cell lineages, 61 broad cell types and 313 subclusters, and identifies 1,085,062 candidate cis-regulatory elements (cCREs), including 161,270 novel elements absent from ENCODE. Regulatory activity was dominated by cell identity but refined by tissue context. Joint profiling enabled 871,177 cCRE-gene associations and revealed lineage-specific regulatory architectures. Cross-tissue accessibility further identified lineage-restricted and constitutively inaccessible chromatin domains, the latter showing preferential hypomethylation across human cancers. Furthermore, we leverage this dataset to train sequence-to-function models to predict chromatin-accessibility effects for 548,656 fine-mapped variants, identifying 18,133 high-effect variants, including 1,120 broadly active variants. Models trained for eight endothelial subtypes further resolve predicted variant effects across vascular beds. Together, this atlas provides a comprehensive cellular and computational framework for interpreting regulatory sequence, context-dependent gene control, and complex trait genetics across the human body.

genomics↗
bioRxiv2026

The chromosome level genome of the Blueberry Stem Gall Wasp, Hemadas nubilipennis (Hymenoptera: Ormyridae) on lowbush blueberry (Vaccinium angustifolium) reveals repeat-driven expansion

Gall-inducing wasps are emerging models for studying plantinsect coevolution, host manipulation, host plant adaptation, and speciation, yet chromosome-level resources remain scarce for most lineages. The blueberry stem gall wasp (BSGW), Hemadas nubilipennis (Hymenoptera: Ormyridae), is native to North America where it induces galls on both lowbush (Vaccinium angustifolium) and highbush blueberries (V. corymbosum). Recently, BSGW has reached outbreak densities in cultivated highbush production. Given that (a) the biology has been characterized primarily from natural lowbush-associated populations, (b) the absence of genomic resources limits comparative analyses, and (c) populations on cultivated highbush represent a recent host shift, we generated the first chromosome-level genome from wild lowbush blueberry. The BSGW genome consists of five chromosome-scale scaffolds totaling 1.08 Gb (N50 = 218 Mb), the second largest known in Chalcidoidea. Comparative analysis reveals that genome size variation is driven primarily by transposable element proliferation (R = 0.96, p < 0.001), with BSGW exhibiting a high proportion of unclassified TEs. Gene-body methylation is conserved, enriched in exons of broadly expressed core genes, and correlates with gene density. The mitochondrial genome (18,697 bp) exhibits extensive gene rearrangement, and COI sequences reveal 4.35.4% divergence from geographically distant populations, suggesting a complex of cryptic species. Additionally, we assemble a near-complete genome of the endosymbiont Wolbachia pipientis (Supergroup A), which encodes PifA and PifB effectors potentially linked to parthenogenesis. These resources establish a foundation for population genomics, taxonomic revision, and applied management, while providing insights into genome architecture, epigenetics, and symbiont interactions.

genomics↗