Pseudomonas aeruginosa can cause life-threatening
infections in immunocompromised patients. The first-line agents to treat P. aeruginosa
infections are
carbapenems. However, the emergence of
carbapenem-resistant P. aeruginosa strains greatly compromised the effectiveness of
carbapenem treatment, which makes the surveillance on their spreading and transmission important. Here we characterized the full-length genomes of two
carbapenem-resistant P. aeruginosa clinical isolates that are capable of producing New Delhi metallo-β-lactamase-1 (NDM-1). We show that bla NDM-1 is carried by a novel integrative and conjugative
element (
ICE) ICETn4371 6385, which also carries the
macrolide resistance gene msr(E) and the
florfenicol resistance gene floR. By exogenously expressing msr(E) in P. aeruginosa laboratory strains, we show that Msr(E) can abolish
azithromycin-mediated quorum sensing inhibition in vitro and anti-Pseudomonas effect in vivo. We conclude that ICEs are important in transmitting
carbapenem resistance, and that anti-virulence treatment of P. aeruginosa
infections using sub-inhibitory concentrations of
macrolides can be challenged by horizontal gene transfer.