Plasmids Shape the Diverse Accessory Resistomes of Escherichia coli ST131

Abstract

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.

Epigenomics, genomics, resistome, mobilome, virulome and evolutionary phylogenomics of carbapenem-resistant Klebsiella pneumoniae clinical strains

“…Recently, environmental bacteria were found to be abundant in Dams with GATC and ATGNNNNNNGCT motifs [43], which were mostly found on chromosomes of this study's isolates. GATC and CCAGG (CCWGG or CCNGG in this study) motifs have been also identified in E. coli [71,83], showing that plasmids with these RMS and methylation signatures can be shared between environmental and clinical prokaryotes. Therefore, the important role of RMS in horizontal resistomes and virulome transmission and regulation cannot be contradicted.…”

“…Notably, the close evolutionary alignment/distance of plasmids bearing he same or different ARGs, but belonging to different incompatibilities in the same isolate (Fig. 7a), indicates the genetic exchanges (recombinations and rearrangements) that occur between plasmids and between plasmids and chromosomes during replication [71,72]. Evidently, the very close sequence and resistome similarity between this study's plasmids and those obtained from different and the same species in other studies worldwide shows the global dissemination of IncF, IncX, A/C, IncN and IncI plasmids and their role in dissemination of ARGs among bacteria.…”

Global evolutionary epidemiology and resistome dynamics of Citrobacter species, Enterobacter hormaechei, Klebsiella variicola, and Proteeae clones

“…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 (Pedersen et al ., 2018; Mbelle et al ., 2019a,b; Mbelle et al ., 2020a; Osei Sekyere et al ., 2020a; Kopotsa et al, 2020). 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 (Chirindze et al ., 2018; Osei Sekyere and Asante, 2018; Pedersen et al ., 2018; Decano et al ., 2020). 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) ( Partridge et al ., 2018 ; Asante and Osei Sekyere, 2019; He et al ., 2019; Li et al ., 2019; Van Boeckel et al ., 2019; Böhm et al ., 2020).…”

“…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) ( Partridge et al ., 2018 ; Asante and Osei Sekyere, 2019; He et al ., 2019; Li et al ., 2019; Van Boeckel et al ., 2019; Böhm et al ., 2020). Thus, such conjugative plasmids influence the genomic plasticity of several related and unrelated species and genera of bacteria (Conlan et al ., 2016; Olaitan et al ., 2016; Jaidane et al ., 2018; Decano et al ., 2019; Decano et al ., 2020; Osei Sekyere et al ., 2020a).…”

“…Coupled with plasmid‐borne dissemination of ARGs is the selection and expansion of specific drug‐resistant clones (Decano et al ., 2019; Decano et al ., 2020), which quickly spread under antibiotic pressure to overpopulate their environments, facilitating their survival and subsequent spread to other environments (Liu et al ., 2018; Asante and Osei Sekyere, 2019; Osei Sekyere et al ., 2020b). 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 (Tshisevhe et al ., 2016; Pedersen et al ., 2018; Kopotsa et al ., 2019; Mbelle et al ., 2019a; Osei Sekyere et al ., 2020a; Mbelle et al ., 2020b).…”