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Insertion sequences (ISs) and other transposable elements are associated with the mobilization of antibiotic resistance determinants and the modulation of pathogenic characteristics. In this work, we aimed to investigate the association between ISs and antibiotic resistance genes, and their role in the dissemination and modification of the antibiotic-resistant phenotype. To that end, we leveraged fully resolved Enterococcus faecium and Enterococcus faecalis genomes of isolates collected over 5 days from an inpatient with prolonged bacteraemia. Isolates from both species harboured similar IS family content but showed significant species-dependent differences in copy number and arrangements of ISs throughout their replicons. Here, we describe two inter-specific IS-mediated recombination events and IS-mediated excision events in plasmids of E. faecium isolates. We also characterize a novel arrangement of the ISs in a Tn1546-like transposon in E. faecalis isolates likely implicated in a vancomycin genotype–phenotype discrepancy. Furthermore, an extended analysis revealed a novel association between daptomycin resistance mutations in liaSR genes and a putative composite transposon in E. faecium , offering a new paradigm for the study of daptomycin resistance and novel insights into its dissemination. In conclusion, our study highlights the role ISs and other transposable elements play in the rapid adaptation and response to clinically relevant stresses such as aggressive antibiotic treatment in enterococci. 

ABSTRACT Here, we report the complete genome sequence of Providencia rettgeri isolate PROV_UAMS_01, which was recovered in 2021 from a urine sample from a hospitalized patient in Arkansas, USA. The genome sequence of P. rettgeri isolate PROV_UAMS_01 comprises a single chromosomal replicon with a G+C content of 40.51% and a total of 3,887 genes. 

Abstract Background VREfm is a major cause of Hospital Acquired Infection in the United States. We analyzed all the VREfm infections that occurred in our institution between 2018 and 2019 using Whole Genome Sequencing (WGS) to understand epidemiological relationship between previously unidentified clusters. In this study we describe a cluster in our hematology oncology unit. Methods A total of 109 discrete VREfm isolates from 66 patients were analyzed. VREfm isolates used in this study were identified from positive blood and urine cultures. Genomic deoxyribonucleic acid (DNA) was extracted from pure cultures. The purity and integrity of extracted DNA were determined using appropriate assays. Library construction and sequencing were conducted and Multi Locust Sequence Typing (MLST) obtained (image 1). Phylogenomic tree was plotted using the Interactive Tree of Life (image 2). Image 1 - methods Image 2 - Tree of Life Results Total of 7 clusters were identified. Here we describe one cluster (image 3) with the highest genetic similarity which showed maximum difference of 5 Single Nucleotide Polymorphisms (zero between patient 1 and 2, image 4). The cluster is composed of 24 clinical strains of VREfm from 6 patients, over a 9 month time period (Image 5). All patients had hematologic malignancies; 4/6 patients had received recent chemotherapy and 5/6 patients were neutropenic. 4 patients were admitted in a single unit (labelled E7), 1 patient was on a sister unit (labelled F7); and 1 patient was in the cancer infusion center. All patients had central venous access placed by radiology at the time of diagnosis of infection and had visited our outpatient infusion center multiple times during this time frame. Image 3 - Close look at cluster 1 Image 4 - Dendrogram of 106 isolates performed with coreSNP(Single Nucleotide Polymorphisms) pairwise distances. • Dendogram shows different patients (same color for isolates that belong to the same patient) and the patient numbers. • Besides the patient number, the number of largest number SNPS that separate those isolates is shown. • Branches represent the number of coreSNPs that differ strains from that branch. As you see isolates from cluster 1 differ in a maximum of 5 SNPs but isolates of patient 1 and patient 2 differ in 0 SNPs between them. Cluster 1 is represented by a green square. Image 5 - Time period of infections Conclusion The prolonged period in our cluster argues in favor of an environmental niche in the hospital unit. We are unable to elucidate pattern of transmission in a cluster of infections without knowing patient colonization of VREfm; because we are likely looking at the tip of the iceberg when analyzing infected cases. It is difficult to ascribe causality to any one of these exposures without concomitant surveillance cultures of environment and personnel. Retrospective WGS is of limited value in infection control. We now have third generation sequencing with the MinION device to do real time sequencing with which we also validated some of our samples. Disclosures Atul Kothari, MD, Ansun Biopharma (Consultant) 

The acute radiation syndrome is defined in large part by radiation injury in the hematopoietic and gastrointestinal (GI) systems. To identify new pathways involved in radiation-induced GI injury, this study assessed dose- and time-dependent changes in plasma metabolites in a nonhuman primate model of whole abdominal irradiation. Male and female adult Rhesus monkeys were exposed to 6 MV photons to the abdomen at doses ranging between 8 and 14 Gy. At time points from 1 to 60 days after irradiation, plasma samples were collected and subjected to untargeted metabolomics. With the limited sample size of females, different discovery times after irradiation between males and females were observed in metabolomics pattern. Detailed analyses are restricted to only males for the discovery power. Radiation caused an increase in fatty acid oxidation and circulating levels of corticosteroids which may be an indication of physiological stress, and amino acids, indicative of a cellular repair response. The largest changes were observed at days 9 and 10 post-irradiation, with most returning to baseline at day 30. In addition, dysregulated metabolites involved in amino acid pathways, which might indicate changes in the microbiome, were detected. In conclusion, abdominal irradiation in a nonhuman primate model caused a plasma metabolome profile indicative of GI injury. These results point to pathways that may be targeted for intervention or used as early indicators of GI radiation injury. Moreover, our results suggest that effects are sex-specific and that interventions may need to be tailored accordingly.