Comparative Genomic Analysis of the ICESa2603 Family ICEs and Spread of erm(B)- and tet(O)-Carrying Transferable 89K-Subtype ICEs in Swine and Bovine Isolates in China

Abstract

Integrative and conjugative elements (ICEs) of the ICESa2603 family have been isolated from several species of Streptococcus spp.; however, the comparative genomic and evolutionary analyses of these particular ICEs are currently only at their initial stages. By investigating 13 ICEs of the ICESa2603 family and two ICESa2603 family-like ICEs derived from diverse hosts and locations, we have determined that ICEs comprised a backbone of 30 identical syntenic core genes and accessory genes that were restricted to the intergenic sites or the 3′-end of the non-conserved domain of core genes to maintain its function. ICESa2603 family integrase IntICESa2603 specifically recognized a 15-bp att sequence (TTATTTAAGAGTAAC) at the 3′-end of rplL, which was highly conserved in genus Streptococcus. Phylogenetic analyses suggest that extensive recombination/insertion and the occurrence of a hybrid/mosaic in the ICESa2603 family were responsible for the significant increase in ICE diversity, thereby broadening its host range. Approximately 42.5 and 38.1% of the tested Streptococcus suis and Streptococcus agalactiae clinical isolates respectively contained ICESa2603 family Type IV secretion system (T4SS) genes, and 80.5 and 62.5% of which also respectively carried intICESa2603, indicating that ICESa2603 family is widely distributed across these bacteria. Sequencing and conjugation transfer of a novel sequence type ST303 clinical S. suis isolate HB1011 demonstrated that the 89K-subtype ICESsuHB1011 retained its transferrable function, thereby conferring tetracycline and macrolide resistance.

Chromosomal Conjugative and Mobilizable Elements in Streptococcus suis: Major Actors in the Spreading of Antimicrobial Resistance and Bacteriocin Synthesis Genes

“…A total of 55 of these AMR genes were found on ICEs. Most of the ICEs carrying AMR genes belong to the Tn5252 family that has already been largely described as AMR genes vehicle in S. suis [12,15]. Some of them carry novel combinations of AMR genes compared to ICEs previously described by Huang et al [13] and Palmieri et al [15].…”

“…In the context of the rising threat of antimicrobial resistance [7,8] requiring a One Health approach, S. suis is receiving growing attention due to its extended drug resistance [9]. Numerous resistance determinants (in particular tetracycline, macrolide, aminoglycoside, and chloramphenicol resistance genes) have been described in this bacterial species, many of them being carried by Integrative Conjugative Elements (ICEs) [10][11][12][13][14][15][16]. ICEs are mobile genetic elements that excise from the chromosome and transfer autonomously by conjugation [17].…”

“…After cleavage at a site called oriT, DNA is addressed to a type IV secretion system by a relaxase, thanks to its interactions with a coupling protein [18]. The main families of ICEs carrying antimicrobial resistance (AMR) genes described in S. suis are Tn916, Tn5252, and Tn1549 families [11][12][13][14][15]19,20]. Mosaic or composite elements resulting from tandem accretions of ICEs or internal insertions of ICEs within another ICE were reported [11][12][13][14][15]19,20].…”

ICE Spy 009, a Conjugative Genetic Element Carrying mef (E) in Streptococcus pyogenes

“…Although the functions of these putative ORFs remain to be elucidated, this region may represent a novel accessory resistance module among those already described for the ICESa2603 family (36).…”

“…This gene encodes hyaluronidase, the enzyme that cleaves the hyaluronic acid (HA) of bacterial capsule and mammalian tissue and permits bacteria to utilize HA as an energy source (37). This represents a novel integration site for an ICE of the ICESa2603 family, for which the most common integration site is the rplL gene (36), and it adds to the list of sites where ICEs encoding tyrosine recombinases can be integrated (23). hylA can represent an alternative integration site for ICESpy009 when rplL is occupied by another integrated element, as in the case of MB56Spyo009.…”