A Novel Integrative Conjugative Element Mediates Genetic Transfer from Group G Streptococcus to Other β-Hemolytic Streptococci

Abstract

ABSTRACT Lateral gene transfer is a significant contributor to the ongoing evolution of many bacterial pathogens, including β-hemolytic streptococci. Here we provide the first characterization of a novel integrative conjugative element (ICE), ICE Sde 3396, from Streptococcus dysgalactiae subsp. equisimilis (group G streptococcus [GGS]), a bacterium commonly found in the throat and skin of humans. ICE Sde 3396 is 64 kb in size and encodes 66 putative open reading frames. ICE Sde 3396 shares 38 open reading frames with a putative ICE from Streptococcus agalactiae (group B streptococcus [GBS]), ICE Sa 2603. In addition to genes involves in conjugal processes, ICE Sde 3396 also carries genes predicted to be involved in virulence and resistance to various metals. A major feature of ICE Sde 3396 differentiating it from ICE Sa 2603 is the presence of an 18-kb internal recombinogenic region containing four unique gene clusters, which appear to have been acquired from streptococcal and nonstreptococcal bacterial species. The four clusters include two cadmium resistance operons, an arsenic resistance operon, and genes with orthologues in a group A streptococcus (GAS) prophage. Streptococci that naturally harbor ICE Sde 3396 have increased resistance to cadmium and arsenate, indicating the functionality of genes present in the 18-kb recombinogenic region. By marking ICE Sde 3396 with a kanamycin resistance gene, we demonstrate that the ICE is transferable to other GGS isolates as well as GBS and GAS. To investigate the presence of the ICE in clinical streptococcal isolates, we screened 69 isolates (30 GGS, 19 GBS, and 20 GAS isolates) for the presence of three separate regions of ICE Sde 3396. Eleven isolates possessed all three regions, suggesting they harbored ICE Sde 3396-like elements. Another four isolates possessed ICE Sa 2603-like elements. We propose that ICE Sde 3396 is a mobile genetic element that is capable of acquiring DNA from multiple bacterial sources and is a vehicle for dissemination of this DNA through the wider β-hemolytic streptococcal population.