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.

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