Mechanism of chromosomal transfer of Enterococcus faecalis pathogenicity island, capsule, antimicrobial resistance, and other traits

Abstract

The Enterococcus faecalis pathogenicity island (PAI) encodes known virulence traits and >100 additional genes with unknown roles in enterococcal biology. Phage-related integration and excision genes, and direct repeats flanking the island, suggest it moves as an integrative conjugative element (ICE). However, transfer was observed not to require these genes. Transfer only occurred from donors possessing a pheromone responsive-type of conjugative plasmid, and was invariably accompanied by transfer of flanking donor chromosome sequences. Deletion of plasmid transfer functions, including the cis -acting origin of transfer ( oriT ), abolished movement. In addition to demonstrating PAI movement by a mechanism involving plasmid integration, we observed transfer of a selectable marker placed virtually anywhere on the chromosome. Transfer of this selectable marker was observed to be accompanied by chromosome-chromosome transfer of vancomycin resistance, MLST markers, and capsule genes as well. Plasmid mobilization therefore appears to be a major mechanism for horizontal gene transfer in the evolution of antibiotic resistant E. faecalis strains capable of causing human infection.

The Plasmidome of Firmicutes: Impact on the Emergence and the Spread of Resistance to Antimicrobials

“…Staphylococcal and enterococcal RepA_N plasmids have greatly contributed to the spread of AbR genes among humans and, eventually, animals and will be further described below. They also facilitate the movement of other nonconjugative plasmids and large genomic regions (36,125,126).…”

“…Megaplasmids of E. faecium or pheromone-responsive E. faecalis plasmids enhance the ability to colonize, invade, and form biofilms (65,126,154). Conjugative plasmids may influence the mobilization of nonconjugative elements and chromosomal regions and facilitate the acquisition of different adaptive traits and genome evolvability (71,125,126). Most enterococcal plasmids are able to acquire and disseminate AbR genes by different mechanisms of genetic exchange.…”

“…Although pheromone plasmids are unable to replicate in S. aureus, their transference and establishment in this host might occur by co-integration with other plasmids able to replicate in this species. In addition, some pAD1 relatives enhance the rate of mobilization of plasmids, conjugative transposons, and PAIs (125). Plasmids of this family can be classified on the basis of responses to pheromones in different incompatibility groups (139) or according to RIP diversity (59,68) within rep 8 (pAM373) and rep 9 (further split into subgroups rep 9a(pAD1) and rep 9b(pTEF2) ) families (59,68).…”

ICE Slu van, a 94-Kilobase Mosaic Integrative Conjugative Element Conferring Interspecies Transfer of VanB-Type Glycopeptide Resistance, a Novel Bacitracin Resistance Locus, and a Toxin-Antitoxin Stabilization System

“…Characterization of V583 PAI transconjugants showed cotransfer of selectable markers representing virtually all regions of the chromosome, including a vancomycin resistance transposon, capsule genes, and alleles which are used for multilocus sequence typing. PAI transfer was dependent upon helper plasmid function in the donors (54).…”

Relevance of the clustered regularly interspaced short palindromic repeats of Enterococcus faecalis strains isolated from retreatment root canals on periapical lesions, resistance to irrigants and biofilms

“…Thus, E. faecalis from a root canal infection may adhere to the bottom of the plates and generate a great deal of biofilm, possibly due to the presence of adhesive proteins. The E. faecalis PAI originates from an exogenous horizontal gene transfer and contains ≥100 additional genes with unknown roles that are possibly associated with the biofilm formation capacity, virulence and drugresistance of E. faecalis (34). Therefore, the CRISPR-cas system is able to prevent mobile gene transfers and E. faecalis gains more virulence factors in the absence of a CRISPR-cas determinant.…”