Plasmids of the IncA and IncC incompatibility group (formerly named as IncA/C) are large (generally >130 kb) low-copy (or possibly single-copy) conjugative extrachromosomal elements that often encode multiple resistance genes (Harmer et al., Carattoli et al.). Historically, the IncA/C complex was created by combining the IncA group (Datta et al.) including RA1 as sole sequenced member with the closely related plasmids of the IncC group. Later, based on their relatedness, IncA and IncC plasmids have been merged and referred as A/C1 and A/C2 subgroups of IncA/C family, respectively. Finally, IncA and IncC plasmids have recently been separated again into two distinct groups due to their compatibility(Ambrose et al.). Unlike IncA group consisting only of RA1 and RA2 (Datta et al.), IncC group is a large family of hundreds of plasmids with conserved backbone and diverse accessory regions. IncC plasmids have two distinct lineages, named type 1 and type 2, which are represented by reference plasmids pR148 (Del Castillo et al.), and pR55 (Doublet et al.), respectively. The two types are characterized based on the alleles of orf1832/1847 and rhs1/2 genes they possess in loci R1 and R2 and the presence of two small insertions (i1 and i2) (Harmer et al.). However, the distinction of these types is sometimes ambiguous due to the lack of one or more markers or to formation of hybrid backbones by recombination (Ambrose et al., Cheng et al.).
| Type | ORF1832 | ORF1847 | RHS1 | RHS2 | I1 | I2 |
|---|---|---|---|---|---|---|
| Type C1 | + | - | + | - | - | - |
| Type C2 | - | + | - | + | + | + |
Comparative genomic studies have revealed that IncA and IncC plasmids have a highly conserved backbone encoding replication, maintenance and conjugation functions, which is interrupted by variable accessory modules (Harmer et al.). The accessory modules are often identified as antibiotic resistance islands (ARIs) that harbor various resistance determinants associated with complex arrays of transposons and integrons (Harmer et al.). IncC plasmids contain ARIs at two specific positions (ARI-A in type 1 and ARI-B in type 1 and 2), though in some family members ARIs can also be found in the rhs-kfrA region. Relatively little is known about the origin of ARIs, but ARI-Bs presumably evolved by incorporation of GIsul2 (Nigro et al.) into the IncC backbone in the early stage of evolution and subsequent internal replacements and rearrangements of the island (Harmer et al., Szabó et al.).
The conjugative transfer system of IncA and IncC plasmids has been classified into the MOBH family (Garcillán-Barcia et al.) including also the IncH, IncJ, IncT and IncP7 groups of plasmids, as well as the SXT family of integrative conjugative elements (ICEs). Owing to their broad host range, an effective conjugative transfer system and the ability to mobilize multidrug-resistant genomic islands (GIs) such as the elements of SGI1 family (Doublet et al.) and several unrelated GIs (Carraro et al., Carraro et al., Rivard et al.), IncA and IncC plasmids efficiently distribute multidrug resistance phenotypes among Gram-negative bacteria.