The human gut microbiome includes beneficial, commensal and pathogenic bacteria that possess antimicrobial resistance (AMR) genes and exchange these predominantly through conjugative plasmids. Escherichia coli is a significant component of the gastrointestinal microbiome and is typically non-pathogenic in this niche. In contrast, extra-intestinal pathogenic E. coli (ExPEC) including ST131 may occupy other environments like the urinary tract or bloodstream where they express genes enabling AMR and host cell adhesion like type 1 fimbriae. The extent to which commensal E. coli and uropathogenic ExPEC ST131 share AMR genes remains understudied at a genomic level, and we examined this here using a preterm infant resistome. We found that individual ST131 had small differences in AMR gene content relative to a larger shared resistome. Comparisons with a range of plasmids common in ST131 showed that AMR gene composition was driven by conjugation, recombination and mobile genetic elements. Plasmid pEK499 had extended regions in most ST131 Clade C isolates, and it had evidence of a co-evolutionary signal based on protein-level interactions with chromosomal gene products, as did pEK204 that had a type IV fimbrial pil operon. ST131 possessed extensive diversity of selective type 1, type IV, P and F17-like fimbriae genes that was highest in subclade C2. The structure and composition of AMR genes, plasmids and fimbriae vary widely in ST131 Clade C and this may mediate pathogenicity and infection outcomes.

Background Some experimental and retrospective clinical studies signal an association between certain anaesthetic techniques and tumour metastasis following breast cancer surgery. Neutrophil Extracellular Trapping (NETosis) is an immunological process, whereby neutrophils engulf tumour antigen then degranulate, leaving a serologic marker. NETosis expression among breast cancer patients is associated with an increased risk of metastasis. We investigated the effect of two distinct anaesthetic techniques on the expression of NETosis in women who underwent potentially curative breast cancer surgery. Methods In a parallel‐group, randomised controlled trial, a subset of women (n = 40) undergoing breast cancer resection surgery, who were partaking in a larger trial (NCT00418457), were randomly assigned to receive volatile general anaesthesia (GA) or propofol GA combined with paravertebral regional anaesthesia (PPA) for their surgery. Serum was taken and stored before and 24 hours post‐operatively. NETosis was measured by ELISA using Neutrophil Myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit) biomarkers, which were the co‐primary end points. Results Patient and breast cancer characteristics did not differ significantly between groups. Recurrence occurred in 7.5% patients. GA patients received more opioids and reported higher post‐operative pain than PPA. There was no difference in post‐operative MPO in GA vs PPA (10.5 ± 6.6 vs 11.5 ± 4.7 ng mL−1, P = .60). Regarding CitH3, there was no difference post‐operatively in GA vs PPA (3.6 ± 2.3 vs 4.0 ± 5.9, P = .80). NET expression did not differ before or after anaesthesia and surgery in either group, for either biomarker. Conclusion Anaesthetic technique did not affect NETosis expression in breast cancer patients, indicating that it is not a viable marker of the effect of anaesthetic technique on breast cancer recurrence.

The human gut microbiome includes beneficial, commensal and pathogenic bacteria that possess antimicrobial resistance (AMR) genes and exchange these predominantly through conjugative plasmids. Escherichia coli is a significant component of the gastrointestinal microbiome and is typically non-pathogenic in this niche. In contrast, extra-intestinal pathogenic E. coli (ExPEC) including ST131 may occupy other environments like the urinary tract or bloodstream where they express genes enabling AMR and host adhesion like type 1 fimbriae. The extent to which non-pathogenic gut E. coli and infectious ST131 share AMR genes and key associated plasmids remains understudied at a genomic level. Here, we examined AMR gene sharing between gut E. coli and ST131 to discover an extensive shared preterm infant resistome. In addition, individual ST131 show extensive AMR gene diversity highlighting that analyses restricted to the core genome may be limiting and could miss AMR gene transfer patterns. We show that pEK499-like segments are ancestral to most ST131 Clade C isolates, contrasting with a minority with substantial pEK204-like regions encoding a type IV fimbriae operon. Moreover, ST131 possess extensive diversity at genes encoding type 1, type IV, P and F17-like fimbriae, particular within subclade C2. The type, structure and composition of AMR genes, plasmids and fimbriae varies widely in ST131 and this may mediate pathogenicity and infection outcomes.

19The human gut microbiome includes beneficial, commensal and pathogenic bacteria that possess 20 antimicrobial resistance (AMR) genes and exchange these predominantly through conjugative 21 plasmids. Escherichia coli is a significant component of the gastrointestinal microbiome and is 22typically non-pathogenic in this niche. In contrast, extra-intestinal pathogenic E. coli (ExPEC) 23including ST131 may occupy other environments like the urinary tract or bloodstream where they 24 express genes enabling AMR and host adhesion like type 1 fimbriae. The extent to which non-25pathogenic gut E. coli and infectious ST131 share AMR genes and key associated plasmids remains 26understudied at a genomic level. Here, we examined AMR gene sharing between gut E. coli and 27 ST131 to discover an extensive shared preterm infant resistome. In addition, individual ST131 show 28 extensive AMR gene diversity highlighting that analyses restricted to the core genome may be limiting 29and could miss AMR gene transfer patterns. We show that pEK499-like segments are ancestral to most 30 ST131 Clade C isolates, contrasting with a minority with substantial pEK204-like regions encoding a 31type IV fimbriae operon. Moreover, ST131 possess extensive diversity at genes encoding type 1, type 32 IV, P and F17-like fimbriae, particular within subclade C2. The type, structure and composition of 33 AMR genes, plasmids and fimbriae varies widely in ST131 and this may mediate pathogenicity and 34 infection outcomes. 35 36

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