First Indian report on Genome-wide Comparison of Multidrug-Resistant Escherichia coli from Blood Stream Infections

Devanga Ragupathi, N. K.; Balaji, V.; Muthuirulandi Sethuvel, D. P.; Anandan, S.; Vasudevan, K.; Neeravi, A. R.; Daniel, J. L. K.; Sathyendra, S.; Iyadurai, R.; Mutreja, A.

doi:10.1101/705905

bioRxiv · 10.1101/705905

First Indian report on Genome-wide Comparison of Multidrug-Resistant Escherichia coli from Blood Stream Infections

Devanga Ragupathi, N. K.·Balaji, V.·Muthuirulandi Sethuvel, D. P.·Anandan, S.·Vasudevan, K.·Neeravi, A. R.·Daniel, J. L. K.·Sathyendra, S.·Iyadurai, R.·Mutreja, A.

View original source ↗Export metadata ↓

Abstract

BackgroundMultidrug-resistant (MDR) E. coli with extended-spectrum {beta}-lactamases (ESBLs) is becoming endemic in health care settings around the world. Baseline data on virulence and AMR of specific lineages of E. coli circulating in developing countries like India is currently lacking.\n\nMethodsWhole-genome sequencing was performed for 60 MDR E. coli isolates. Genome-wide analysis was performed at single nucleotide polymorphism (SNP) level resolution to identify the relation between the isolates in context of time, virulence and AMR determinants possessed.\n\nResultsGenome comparison revealed the presence of ST-131 global MDR and ST410 as emerging-MDR clades of E. coli. AMR gene profile for cephalosporin and carbapenem resistance differed between the clades. Genotypes blaCTX-M-15 and blaNDM-5 were common among cephalosporinases and carbapenemases, respectively. For aminoglycoside resistance, rmtB was positive for 31.7% of the isolates, of which 30% were co-harboring carbapenemases. Further, the FimH types and virulence gene profile positively correlated with the SNP based phylogeny, which also revealed the evolution of MDR clones among the study population with temporal accumulation of SNPs. The predominant clone was ST167 (blaNDM lineage) followed by ST405 (global clone ST131 equivalent) and ST410 (fast spreading high risk clone).\n\nConclusionsThis is the first report on the whole genome analysis of MDR E. coli lineages circulating in India. Data from this study will provide public health agencies a baseline portfolio of AMR and virulence in pathogenic E. coli in the region.

Source connections

Published article ↗

Explore related subjects

genomics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Devanga Ragupathi, N. K., Balaji, V., Muthuirulandi Sethuvel, D. P., Anandan, S., Vasudevan, K., Neeravi, A. R., Daniel, J. L. K., Sathyendra, S., Iyadurai, R., Mutreja, A.. 2019-07-17. First Indian report on Genome-wide Comparison of Multidrug-Resistant Escherichia coli from Blood Stream Infections. https://doi.org/10.1101/705905

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

KEEP EXPLORING

Related preprints

bioRxiv2026

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↗

bioRxiv2026

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↗

bioRxiv2026

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↗