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Constantinides, B.

Publications and source records attributed to Constantinides, B..

2 recordsLinked to original sources

Multi-omic surveillance of Escherichia coli and Klebsiella spp. in hospital sink drains and patients

Escherichia coli and Klebsiella spp. are important human pathogens that cause a wide spectrum of clinical disease. In healthcare settings, sinks and other wastewater sites have been shown to be reservoirs of antimicrobial-resistant E. coli and Klebsiella spp., particularly in the context of outbreaks of resistant strains amongst patients. Without focusing exclusively on resistance markers or a clinical outbreak, we demonstrate that many hospital sink drains are abundantly and persistently colonised with diverse populations of E. coli, Klebsiella pneumoniae and Klebsiella oxytoca, including both antimicrobial-resistant and susceptible strains. Using whole genome sequencing (WGS) of 439 isolates, we show that environmental bacterial populations are largely structured by ward and sink, with only a handful of lineages, such as E. coli ST635, being widely distributed, suggesting different prevailing ecologies which may vary as a result of different inputs and selection pressures. WGS of 46 contemporaneous patient isolates identified one (2%; 95% CI 0.05-11%) E. coli urine infection-associated isolate with high similarity to a prior sink isolate, suggesting that sinks may contribute to up to 10% of infections caused by these organisms in patients on the ward over the same timeframe. Using metagenomics from 20 sink-timepoints, we show that sinks also harbour many clinically relevant antimicrobial resistance genes including blaCTX-M, blaSHV and mcr, and may act as niches for the exchange and amplification of these genes. Our study reinforces the potential role of sinks in contributing to Enterobacterales infection and antimicrobial resistance in hospital patients, something that could be amenable to intervention. IMPORTANCEEscherichia coli and Klebsiella spp. cause a wide range of bacterial infections, including bloodstream, urine and lung infections. Previous studies have shown that sink drains in hospitals may be part of transmission chains in outbreaks of antimicrobial-resistant E. coli and Klebsiella spp., leading to colonisation and clinical disease in patients. We show that even in non-outbreak settings, contamination of sink drains by these bacteria is common across hospital wards, and that many antimicrobial resistance genes can be found and potentially exchanged in these sink drain sites. Our findings demonstrate that the colonisation of handwashing sink drains by these bacteria in hospitals is likely contributing to some infections in patients, and that additional work is needed to further quantify this risk, and to consider appropriate mitigating interventions.

microbiology

The role of CAPG in molecular communication between the embryo and the uterine endometrium: Is its function conserved in species with different implantation strategies?

During the pre-implantation period of pregnancy in eutherian mammals, changes to the uterine endometrium are required (both at the transcriptional and protein level) to facilitate the endometrium becoming receptive to an implanting embryo. We know that the developing conceptus (embryo and extraembryonic membranes) produces proteins during this developmental stage. We hypothesised that this common process in early pregnancy in eutheria may be facilitated by highly conserved conceptus-derived proteins such as macrophage capping protein CAPG. More specifically, we propose that CAPG may share functionality in modifying the transcriptome of the endometrial epithelial cells to facilitate receptivity to implantation in species with different implantation strategies, such as human and bovine. A recombinant bovine form of CAPG (91% sequence identity between bovine and human) was produced and bovine endometrial epithelial (bEECs) and stromal (bESCs) cells and human endometrial epithelial cells (hEECs) were cultured for 24 h with or without rbCAPG. RNA sequencing and quantitative real-time PCR analysis was used to assess the transcriptional response to rbCAPG (Control, vehicle, CAPG 10, 100, 1000 ng/ml: n=3 biological replicates per treatment per species). Treatment of bEECs with CAPG resulted in changes to 1052 transcripts (629 increased and 423 decreased) compared to vehicle controls, including those previously only identified as regulated by interferon-tau, the pregnancy recognition signal in cattle. Treatment of hEECs with bovine CAPG increased expression of transcripts previously known to interact with CAPG in different systems (CAPZB, CAPZA2, ADD1 and ADK) compared with vehicle controls (P<0.05). In conclusion, we have demonstrated that CAPG, a highly conserved protein in eutherian mammals elicits a transcriptional response in the endometrial epithelium in two species with different implantation strategies that may facilitate uterine receptivity.

physiology