Exploring the Accessory Genome of Multidrug-Resistant Rhodococcus equi Clone 2287

Decades of antimicrobial overuse to treat respiratory disease in foals have promoted the emergence and spread of zoonotic multidrug-resistant (MDR) Rhodococcus equi worldwide. Three main R. equi MDR clonal populations-2287, G2106, and G2017-have been identified so far. However, only clones 2287 and G2016 have been isolated from sick animals, with clone 2287 being the main MDR R. equi recovered. The genetic mechanisms that make this MDR clone superior to the others at infecting foals are still unknown. Here, we performed a deep genetic characterization of the accessory genomes of 207 R. equi isolates, and we describe IME2287, a novel genetic element in the accessory genome of clone 2287, potentially involved in the maintenance and spread of this MDR population over time. IME2287 is a putative self-replicative integrative mobilizable element (IME) carrying a DNA replication and partitioning operon and genes encoding its excision and integration from the R. equi genome via a serine recombinase. Additionally, IME2287 encodes a protein containing a Toll/interleukin-1 receptor (TIR) domain that may inhibit TLR-mediated NF-kB signaling in the host and a toxin-antitoxin (TA) system, whose orthologs have been associated with antibiotic resistance/tolerance, virulence, pathogenicity islands, bacterial persistence, and pathogen trafficking. This new set of genes may explain the success of clone 2287 over the other MDR R. equi clones.