Evolution and typing of IncC plasmids contributing to antibiotic resistance in Gram-negative bacteria

Abstract

The large, broad host range IncC plasmids are important contributors to the spread of key antibiotic resistance genes and over 200 complete sequences of IncC plasmids have been reported. To track the spread of these plasmids accurate typing to identify the closest relatives is needed. However, typing can be complicated by the high variability in resistance gene content and various typing methods that rely on features of the conserved backbone have been developed. Plasmids can be broadly typed into two groups, type 1 and type 2, using four features that differentiate the otherwise closely related backbones. These types are found in many different countries in bacteria from humans and animals. However, hybrids of type 1 and type 2 are also occasionally seen, and two further types, each represented by a single plasmid, were distinguished. Generally, the antibiotic resistance genes are located within a small number of resistance islands, only one of which, ARI-B, is found in both type 1 and type 2. The introduction of each resistance island generates a new lineage and, though they are continuously evolving via the loss of resistance genes or introduction of new ones, the island positions serve as valuable lineage-specific markers. A current type 2 lineage of plasmids is derived from an early type 2 plasmid but the sequences of early type 1 plasmids include features not seen in more recent type 1 plasmids, indicating a shared ancestor rather than a direct lineal relationship. Some features, including ones essential for maintenance or for conjugation, have been examined experimentally.

Cocarriage of Distinct bla KPC-2 and bla OXA-48 Plasmids in a Single Sequence Type 11 Carbapenem-Resistant Klebsiella pneumoniae Isolate

“…Because KPC160111 was an ST11_KL47/OL101 strain related to other KPC-2 K. pneumoniae (3), the acquisition of pOXA48-L111, which brought the second carbapenemase OXA-48 into an already KPC-2 background, was suggested as a likely scenario for the emergence of this K. pneumoniae that carried both bla KPC-2 and bla OXA-48 . Besides the carriage of the KPC-2 and OXA-48 plasmids, KPC160111 harbored a novel IncC plasmid (194,181 bp), which exhibited hybrid type 1 and type 2 IncC backbone features (8), and had 4 mosaic cassettes holding a total of 25 AMR genes (see Fig. S3).…”

Genetic and Biochemical Characterization of VMB‐1, a Novel Metallo‐β‐Lactamase Encoded by a Conjugative, Broad‐Host Range IncC Plasmid from Vibrio spp

“…Nevertheless, pVb1796 also contains orf1847, a key feature of type 2 IncC plasmids (Figure S1a, Supporting Information). Remarkably, compared to the plasmid sequences available in GenBank,13 pVb1796 is the only plasmid that carries features of both type 1 and 2 IncC plasmids.…”

“…At present, we expect that the bla VMB‐1 gene remains rarely detectable in clinical Enterobacteriaceae isolates as it takes time for transmission of this new antimicrobial resistance gene from the environmental strains to common human pathogens. However, association of the bla VMB‐1 gene with IncC group plasmids implies a high risk of dissemination of such resistance gene as IncC group plasmids have been identified in bacterial strains of various species recovered from both the environment and clinical setting,12,31 with over 200 sequences of IncC plasmids having been reported or deposited in the GenBank since the first report of such plasmid in 2007 13. IncC plasmid was first described among multidrug resistant Aeromonas hydrophila causing disease in cultured fish in the 1970s, when it was combined with IncA plasmids into IncA/C group 32.…”

Entry Exclusion of Conjugative Plasmids of the IncA, IncC, and Related Untyped Incompatibility Groups

“…IncC and IncA plasmids were long suspected to exclude each other's entry, but the genetic determinants responsible for exclusion were unknown (22)(23)(24)(25). Confusion between exclusion and incompatibility has plagued the nomenclature and typing of these plasmids since the late 1980s (26,31). Nevertheless, Ambrose et al (26) recently confirmed that IncA and IncC replicons are compatible and that the apparent incompatibility between these two plasmid groups most likely resulted from entry exclusion.…”

“…IncC plasmids have been typed in two main groups, type 1 and type 2, based on differences within the resistance gene clusters or loss of backbone regions adjacent to them (1). Hybrid plasmids that share features of both types have also been described, as well as subtypes 1a and 1b, which differ by the presence or absence of a 14.5-kb diverged segment (31). We found no clear correlation between IncC plasmid type and the variant of the eexC gene that they carry.…”