title: ICESpy009, a Conjugative Genetic Element Carrying mef(E) in Streptococcus pyogenes.
abstract: Efflux-mediated macrolide resistance due to mef(E) and mel, carried by the mega element, is common in Streptococcus pneumoniae, for which it was originally characterized, but it is rare in Streptococcus pyogenes In S. pyogenes, mega was previously found to be enclosed in Tn2009, a composite genetic element of the Tn916 family containing tet(M) and conferring erythromycin and tetracycline resistance. In this study, S. pyogenes isolates containing mef(E), apparently not associated with other resistance determinants, were examined to characterize the genetic context of mega. By whole-genome sequencing of one isolate, MB56Spyo009, we identified a novel composite integrative and conjugative element (ICE) carrying mega, designated ICESpy009, belonging to the ICESa2603 family. ICESpy009 was 55 kb long, contained 61 putative open reading frames (ORFs), and was found to be integrated into hylA, a novel integration site for the ICESa2603 family. The modular organization of the ICE was similar to that of members of the ICESa2603 family carried by different streptococcal species. In addition, a novel cluster of accessory resistance genes was found inside a region that encloses mega. PCR mapping targeting ICESpy009 revealed the presence of a similar ICE in five other isolates under study. While in three isolates the integration site was the same as that of ICESpy009, in two isolates the ICE was integrated into rplL, the typical integration site of the ICESa2603 family. ICESpy009 was able to transfer macrolide resistance by conjugation to both S. pyogenes and S. pneumoniae, showing the first evidence of the transferability of mega from S. pyogenes.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy maria.delgrosso@iss.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Grosso
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Camilli
authors.affiliation: Italian National Research Council, Institute for Biomedical Technologies, Milan, Italy.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Rizzi
authors.affiliation: Italian National Research Council, Institute for Biomedical Technologies, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pietrelli
authors.affiliation: Italian National Research Council, Institute for Biomedical Technologies, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: De Bellis
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pantosti
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004251:DNA Transposable Elements / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004917:Erythromycin / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000235:genetics*; D013753:Tetracycline Resistance / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements; D018942:Macrolides; D004917:Erythromycin