Endometrial receptivity: miRNAs signing in?

Editoria

Prevalence of insertion sequence elements in plasmids relating to mgrB gene disruption causing colistin resistance in Klebsiella pneumoniae

Colistin is a last resort antibiotic for the treatment of carbapenemase producing Klebsiella pneumoniae (CRKP). The disruption of the mgrB gene by insertion sequences (ISs) is a mechanism mediating colistin resistance. Plasmids encode mobilizable IS elements which integrate into the mgrB gene in K. pneumoniae causing gene inactivation and colistin resistance. The species prevalence of mgrB-gene disrupting insertion elements ISL3 (ISKpn25), IS5 (ISKpn26), ISKpn14 and IS903B present on plasmids were assessed. IS containing plasmids were also scanned for antimicrobial resistance genes, including carbapenem resistant genes. Plasmids encoding insertion sequences are abundant in K. pneumoniae. IS903B was found in 28 unique Inc groups, while ISKpn25 was largely carried by IncFIB(pQil) plasmids. ISKpn26 and ISKpn14 were most often found associated with IncFII(pHN7A8) plasmids. Of the 34 unique countries which contained any of the IS elements, ISKpn25 was identified from 26. ISKpn26, ISKpn14, and IS903B insertion sequences were identified from 89.3%, 44.9% and 23.9% plasmid samples from China. Plasmids carrying ISKpn25, ISKpn14, and ISKpn26 IS have a 4.6, 6.0, and 6.6-fold higher carbapenemase gene count respectively, relative to IS903B-carrying plasmids. IS903B bearing plasmids have a 20, 5, and 5-fold higher environmental source isolation count relative to ISKpn25, ISKpn14, and ISKpn26 bearing plasmids. ISKpn25 present on IncFIB(pQil) sourced from clinical settings is established across multiple countries, while ISKpn26, ISKpn14, and IS903B appear most often in China. Carbapenemase presence in tandem with IS elements may help promote an extensively drug resistant profile in K. pneumoniae limiting already narrow therapeutic treatment options

The Presence of an ESBL-Encoding Plasmid Reported During a Klebsiella pneumoniae Nosocomial Outbreak in the United Kingdom

An EBSL-encoding plasmid, pESBL-PH, was identified during a nosocomial outbreak of Klebsiella pneumoniae ST628 at a United Kingdom general district hospital in 2018. The plasmid from the earliest 2018 K. pneumoniae strain discovered during the outbreak was assembled using both Oxford nanopore long reads and illumina short reads, yielding a fully closed plasmid, pESBL-PH-2018. pESBL-PH-2018 was queried against the complete NCBI RefSeq Plasmid Database, comprising 93,823 plasmids, which was downloaded on 16 July 2024. To identify structurally similar plasmids, strict thresholds were applied, including a mash similarity ≥0.98. This returned 61 plasmids belonging to 13 unique sequence types (STs) hosts. The plasmids were detected from 13 unique countries, dating from 2012 to 2023. The AMR region of the plasmids varied. Interestingly IS26-mediated tandem amplification of resistance genes, including the ESBL gene blaCTX-M-15 was identified in two independent strains, raising their copy number to three. Furthermore, the genomic background of strains carrying a pESBL-PH-2018-like plasmid were analyzed, revealing truncation of the chromosomal ompK36 porin gene and carbapenem resistance gene carriage on accessory plasmids in 17.85% and 26.78% of strains with a complete chromosome available. This analysis reveals the widespread dissemination of an ESBL-encoding plasmid in a background of resistance-encoding strains, requiring active surveillance

Summary of data from QuantiFERON-CMV, CMV antibody and flow cytometry assays

Data from 11 healthy volunteers who were subsequently tested by the QuantiFERON-CMV assay, CMV antibody and flow cytometry assays. Each volunteer has been anonymised and all corresponding data is present in this file

Genomic instability and the link to infertility: A focus on microsatellites and genomic instability syndromes.

Infertility is associated to multiple types of different genomic instabilities and is a genetic feature of genomic instability syndromes. While the mismatch repair machinery contributes to the maintenance of genome integrity, surprisingly its potential role in infertility is overlooked. Defects in mismatch repair mechanisms contribute to microsatellite instability and genomic instability syndromes, due to the inability to repair newly replicated DNA. This article reviews the literature to date to elucidate the contribution of microsatellite instability to genomic instability syndromes and infertility. The key findings presented reveal microsatellite instability is poorly researched in genomic instability syndromes and infertility

Endometriosis - on the intersection of modern environmental pollutants and ancient genetic regulatory variants

Endometriosis is a chronic, estrogen-driven inflammatory disorder affecting approximately 10% of reproductive-aged women globally. Despite increasing genomic insights into advanced-stage disease, the genetic underpinnings of early-stage endometriosis remain poorly understood, limiting opportunities for timely diagnosis and intervention. This study explores the contribution of regulatory variants, including those derived from ancient hominin introgression, and their interaction with modern environmental exposures in shaping endometriosis susceptibility. We conducted a dual-phase literature review to identify genes implicated in endometriosis pathophysiology and endocrine-disrupting chemical (EDC) sensitivity. Five genes (IL-6, CNR1, IDO1, TACR3, and KISS1R) were selected based on tissue expression, pathway involvement, and EDC reactivity. Whole-genome sequencing (WGS) data from the Genomics England 100,000 Genomes Project were analysed in nineteen females with clinically confirmed endometriosis. Variant enrichment, co-localisation, and linkage disequilibrium analyses were conducted, and functional impact was evaluated using public regulatory databases. Six regulatory variants were significantly enriched in the endometriosis cohort compared to matched controls and the general Genomics England population. Notably, co-localised IL-6 variants rs2069840 and rs34880821—located at a Neandertal-derived methylation site—demonstrated strong linkage disequilibrium and potential immune dysregulation. Variants in CNR1 and IDO1, some of Denisovan origin, also showed significant associations. Several of these variants overlapped EDC-responsive regulatory regions, suggesting gene-environment interactions may exacerbate risk. These findings propose a novel perspective of endometriosis susceptibility, in which ancient regulatory variants and contemporary environmental exposures converge to modulate immune and inflammatory responses. This integrative approach identified new potential biomarkers for early-stage detection of endometriosis

Genomic analyses of an Escherichia coli and Klebsiella pneumoniae urinary tract co‐infection using long‐read nanopore sequencing.

Escherichia coli (E.coli) and Klebsiella pneumoniae (K. pneumoniae) isolates presenting with the same antimicrobial susceptibility profile were recovered from the same catheter sample of urine (CSU). Both strains were recovered from a patient with a long-standing indwelling urinary catheter. Each isolate had their DNA extracted following culture. Nanopore long-read sequencing was used to build the plasmids and chromosomes from each strain to closure to discern potential horizontal propagation of resistance-encoding plasmids and the relationship between resistance genes and insertion sequences. Plasmids derived from resistance strains in the urinary microbiota remain poorly characterized. The same 11 antimicrobial resistance (AMR) genes were found in plasmids from each strain. The 185,239-bp FIB(K) pKBM1, from the K. pneumoniae strain additionally encoded the 5 AMR genes: sul2, strA, strB, blaTEM-1B, and blaCTX-M-15. A multimeric array of AMR genes and IS26 insertions sequences were found in the plasmids from both isolates. Both plasmids from each isolate were similar. Horizontal transfer of plasmids, followed by subsequent plasmid rearrangement is likely to have occurred during the course of infection. Furthermore, the resistance region in the plasmids shared similarity against the internationally prevalent plasmid, pKPN3-307_typeA, commonly identified in K. pneumoniae ST307. Biofilm formation in catheterized patients may allow close cell-contact between strains. Horizontal propagation of resistance genes may occur, leading to polymicrobial infections