The Significance of Epidemic Plasmids in the Success of Multidrug-Resistant Drug Pandemic Extraintestinal Pathogenic Escherichia coli

Abstract

Epidemic IncF plasmids have been pivotal in the selective advantage of multidrug-resistant (MDR) extraintestinal pathogenic Escherichia coli (ExPEC). These plasmids have offered several advantages to their hosts that allowed them to coevolve with the bacterial host genomes and played an integral role in the success of ExPEC. IncF plasmids are large, mosaic, and often contain various types of antimicrobial resistance (AMR) and virulence associated factor (VAF) genes. The presence of AMR, VAF genes, several addition/restriction systems combined with truncated transfer regions, led to the fixation of IncF plasmids in certain ExPEC MDR clones, such as ST131 and ST410. IncF plasmids entered the ST131 ancestral lineage in the mid 1900s and different ST131 clade/CTX-M plasmid combinations coevolved over time. The IncF_CTX-M-15/ST131-C2 subclade combination emerged during the early 2000s, spread rapidly across the globe, and is one of the greatest clone/plasmid successes of the millennium. The ST410-B3 subclade containing bla CTX-M-15 incorporated the NDM-5 carbapenemase gene into existing IncF platforms, providing an additional positive selective advantage that included the carbapenems. A ''plasmid-replacement'' clade scenario occurred in the histories of ST131 and ST410 as different subclades gained different AMR genes on different IncF platforms. The use of antimicrobial agents will generate selection pressures that enhance the risks for the continuous emergence of MDR ExPEC clone/IncF plasmid combinations. The reasons for clade/IncF replacements and associations between certain clades and specific IncF plasmid types are unknown. Such information will aid in designing management and prevention strategies to combat AMR.

Long read sequencing provides an insight into plasmids found among carbapenemase producingEnterobacteralesfrom hospitals in the United Kingdom during 2021 to 2023

“…The remaining isolates carrying bla NDM-5 were both representatives of E. coli ST167 with multi-replicon IncF (IncFIA /IncFIB(AP001918)/IncFII ) bla NDM-5 plasmids (e.g. CP133853 ) widely found in this organism [9, 10, 11]; they were highly similar to one another, one of 143.5 kb and the other of 141.9 kb, both with bla NDM-5 , aac(6’)-Ib-cr, aadA2, sul1, dfrA12, sitABCD, tet(A), bla CTX-M-15 , bla OXA-1 , mph(A) , truncated qacE and catB3 (ES3_WM2_48.22_ST167_NDM5 and ES4_WM2_48.22_ST167_NDM5).…”

“…The rise in frequency of this NDM variant, particularly in E. coli , but also in K. pneumoniae , has been marked and has been noted by many authors [9, 10, 11]. Our set included two representatives of E. coli ST167 with multi-replicon IncF plasmids carrying bla NDM-5 (e.g.…”

CRISPR-Cas9-mediated IncF plasmid curing in extraintestinal pathogenic Escherichia coli

“…IncF plasmids are large (>50 kb), mosaic, and contain antimicrobial resistance (AMR) genes, virulence associated factor genes, various addiction, restriction, and truncated transfer systems ( 2 ). The presence of addition/restriction systems, combined with truncated transfer regions, has led to IncF plasmid persistence with subsequent fixation within certain ExPEC lineages ( 3 ).…”

Sporadic clone Escherichia coli ST615 as a vector and reservoir for dissemination of crucial antimicrobial resistance genes

“…Simultaneously, some lineages have developed into a pathogen well adapted to their host causing different diseases ( Geurtsen et al., 2022 ), including adaptation to the nosocomial niche as high-risk clones or “superbugs” that rapidly evolve to extreme drug resistance (XDR). The lineage represented by sequence type (ST) 131 is the predominant isolate of hospital infections worldwide among E. coli strains that behave like an epidemic clone, also known as pandemic clones ( Pitout and DeVinney, 2017 ; Soncini et al., 2022 ; Pitout and Chen, 2023 ). On the other hand, little is known about the role of sporadic clones of this species in the adaptation to multidrug resistance among clinical isolates.…”