Diversity and Global Distribution of IncL/M Plasmids Enabling Horizontal Dissemination ofβ-Lactam Resistance Genes among the Enterobacteriaceae

Abstract

Antibiotic resistance determinants are frequently associated with plasmids and other mobile genetic elements, which simplifies their horizontal transmission. Several groups of plasmids (including replicons of the IncL/M incompatibility group) were found to play an important role in the dissemination of resistance genes encoding β-lactamases. The IncL/M plasmids are large, broad host range, and self-transmissible replicons. We have identified and characterized two novel members of this group: pARM26 (isolated from bacteria inhabiting activated sludge from a wastewater treatment plant) and pIGT15 (originating from a clinical strain of Escherichia coli). This instigated a detailed comparative analysis of all available sequences of IncL/M plasmids encoding β-lactamases. The core genome of these plasmids is comprised of 20 genes with conserved synteny. Phylogenetic analyses of these core genes allowed clustering of the plasmids into four separate groups, which reflect their antibiotic resistance profiles. Examination of the biogeography of the IncL/M plasmids revealed that they are most frequently found in bacteria of the family Enterobacteriaceae originating from the Mediterranean region and Western Europe and that they are able to persist in various ecological niches even in the absence of direct antibiotic selection pressure.

Genome-based insights into the resistome and mobilome of multidrug-resistant Aeromonas sp. ARM81 isolated from wastewater

“…(Maj et al 2013) or Psychrobacter spp. (Dziewit et al 2013)] or belonging to a particular incompatibility group [e.g., IncL/M plasmids (Adamczuk et al 2015)], which supports the hypothesis that there is a clear distinction between the permanent members (genes) constituting plasmid backbones and the operative genes (additional load) that can be exchanged between replicating elements in the cell and are not conserved elements of plasmids (Norman et al 2009). …”

Recent independent emergence of multiple multidrug-resistantSerratia marcescensclones within the United Kingdom and Ireland

“…The tetA5 gene also accounted for the elevated resistance to minocycline in 16 samples and appears to be inserted within the chromosome (Table 1). The tetA3 efflux gene, however, was found in the context of the pIGT15 plasmid, which originates from a clinical Escherichia coli isolate (Adamczuk et al 2015). The presence of tetracycline transporter tet41 in some isolates across the tree did not affect the susceptibility to tetracylines.…”

The rapid spread of carbapenem-resistant Enterobacteriaceae

“…Genomic characterization of IncL and IncM plasmid identified high nucleotide conservation (~94%) but two distinct branches when clustered for sequence similarity [Carattoli 2015]. Of 20 IncL/M plasmids sequenced by 2015, 18 harbored β-lactamases from ambler classes A–D including KPC, NDM, VIM, and OXA carbapenemases [Adamczuk 2015]. These plasmid types were originally endemic to the Mediterranean region but have become globally disseminated [Adamczuk 2015].…”

“…Of 20 IncL/M plasmids sequenced by 2015, 18 harbored β-lactamases from ambler classes A–D including KPC, NDM, VIM, and OXA carbapenemases [Adamczuk 2015]. These plasmid types were originally endemic to the Mediterranean region but have become globally disseminated [Adamczuk 2015]. IncL/M plasmids containing bla OXA-48 were demonstrated to have a 40-fold higher transfer efficiency compared to plasmids with bla NDM-1 due to insertion of bla OXA-48 and its flanking transposon Tn1999 into the transfer inhibition protein gene [Potron 2014].…”