Details

Autor(en) / Beteiligte

• Álvarez-Narváez, Sonsiray
• Giguère, Steeve
• Anastasi, Elisa
• Hearn, Jack
• Scortti, Mariela
• Vázquez-Boland, José A
• Buchrieser, Carmen

Titel

Clonal Confinement of a Highly Mobile Resistance Element Driven by Combination Therapy in Rhodococcus equi

Ist Teil von

• mBio, 2019-10, Vol.10 (5)

Ort / Verlag

United States: American Society for Microbiology

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Antibiotic use has been linked to changes in the population structure of human pathogens and the clonal expansion of multidrug-resistant (MDR) strains among healthcare- and community-acquired infections. Here we present a compelling example in a veterinary pathogen, , the causative agent of a severe pulmonary infection affecting foals worldwide. We show that the (46) gene responsible for emerging macrolide resistance among equine isolates in the United States is part of a 6.9-kb transposable element, Tn , actively mobilized by an IS family transposase. Tn is carried on an 87-kb conjugative plasmid, pRErm46, transferable between strains at frequencies up to 10 The (46) gene becomes stabilized in by pRErm46's apparent fitness neutrality and wholesale Tn transposition onto the host genome. This includes the conjugally exchangeable pVAPA virulence plasmid, enabling the possibility of cotransfer of two essential traits for survival in macrolide-treated foals in a single mating event. Despite its high horizontal transfer potential, phylogenomic analyses show that (46) is paradoxically confined to a specific clone, 2287. 2287 also carries a unique mutation conferring high-level resistance to rifampin, systematically administered together with macrolides against rhodococcal pneumonia on equine farms. Our data illustrate that under sustained combination therapy, several independent "founder" genetic events are concurrently required for resistance, limiting not only its emergence but also, crucially, horizontal spread, ultimately determining multiresistance clonality. MDR clades arise upon acquisition of resistance traits, but the determinants of their clonal expansion remain largely undefined. Taking advantage of the unique features of infection control in equine farms, involving the same dual antibiotic treatment since the 1980s (a macrolide and rifampin), this study sheds light into the determinants of multiresistance clonality and the importance of combination therapy in limiting the dissemination of mobile resistance elements. Clinically effective therapeutic alternatives against foal pneumonia are currently lacking, and the identified macrolide-rifampin MDR clone 2287 has serious implications. Still at early stages of evolution and local spread, 2287 may disseminate globally, posing a significant threat to the equine industry and, also, public health due to the risk of zoonotic transmission. The characterization of the 2287 clone and its resistance determinants will enable targeted surveillance and control interventions to tackle the emergence of MDR .