Plasmids shape the diverse accessory resistomes of Escherichia coli ST131

Abstract

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

Global evolutionary epidemiology, phylogeography and resistome dynamics of Citrobacter species, Enterobacter hormaechei, Klebsiella variicola, and Proteeae clones: A One Health analyses

“…Hence, these opportunistic pathogens demand more attention than they have been given hitherto as the rich resistome repertoire identified in their genomes makes them reservoirs of ARGs 11,14,21,43 . Moreover, being intestinal denizens and commensals, they can easily share these ARGs with facultative and obligate pathogens of humans and animals 22,44–46 .…”

“…Conjugative plasmids have been implicated in the transmission of several resistance determinants within and across species, resulting in the presence of same or very similar resistomes in same and different species and clones 1,4,7–9 . Thus, the emergence of plasmid-borne resistance genes is always a cause for concern as they help breach the species barrier and shuttle resistance genes (ARGs) from commensals and non-pathogenic bacteria to pathogenic ones or vice versa 3,4,10,11 . Such has been the case with the emergence and rapid spread of extended-spectrum β-lactamases (ESBLs) viz., TEM, SHV, OXA and CTX-M, carbapenemases such as NDM, IMP, VIM, KPC and GES, the mobile colistin resistance gene mcr-1 (to mcr-10 ) and recently, the mobile tigecycline resistance gene, tet ( X ) 12–17 Thus, such conjugative plasmids influence the genomic plasticity of several related and unrelated species and genera of bacteria 8,11,18–21 .…”

“…Coupled with plasmid-borne dissemination of ARGs is the selection and expansion of specific drug-resistant clones 11,21 , which quickly spread under antibiotic pressure to overpopulate their environments, facilitating their survival and subsequent spread to other environments 14,22,23 . In cases where such clones harbour resistance plasmids, their expansion almost always lead to the concomitant replication and intra-clonal as well as inter-clonal spread of such plasmids 4,5,7,8,24,25 Thus, as such clones are disseminated through contact, food, water, farms, hospitals, and the environment, they carry with them these resistance plasmids to colonize new hosts and environments 6,26–28 .…”

“…and Providencia spp . are not mostly reported as Escherichia coli, Klebsiella pneumoniae , and Salmonella enterica , they have been associated with multiple resistance and clinical fatalities 3,7,14,25,28,34 Due to the transferability of resistance plasmids between members of the Enterobacteriaceae, the global resistome epidemiology of these six genera is important as they could be eventually transferred to commonly isolated Enterobacteriaceae species 11,14,21,25,35,36 .…”

Epigenomics, Genomics, Resistome, Mobilome, Virulome and Evolutionary Phylogenomics of Carbapenem-resistant Klebsiella pneumoniae clinical strains

“…Notably, the close evolutionary alignment/distance of plasmids bearing same or different ARGs, but belonging to different incompatibilities in the same isolate (Fig. 7a), depicts the genetic exchanges (recombinations and rearrangements) that occur between plasmids and between plasmids and chromosomes during replication 59,60 . Evidently, the very close sequence and resistome similarity between this study’s plasmids and those obtained from different and same species in other studies worldwide portrays the global dissemination of IncF, IncX, A/C, IncN, and IncI plasmids and their role in ARGs dissemination among bacteria.…”