Dissemination of Pseudomonas aeruginosa bla NDM-1 -Positive ST308 Clone in Singapore.

Pseudomonas aeruginosa ST308 clone has been reported to carry carbapenemase genes such as bla IMP and bla VIM but has been rarely associated with bla NDM-1 . A total of 199 P. aeruginosa ST308 clinical and environmental isolates obtained between April 2019 and November 2020 from a tertiary-care hospital in Singapore were characterized using whole-genome sequencing. In addition, 71 bla NDM-1 -positive ST308 whole-genome sequences from two other local tertiary-care hospitals in Singapore and 83 global bla NDM-1 -negative ST308 whole-genome sequences in public databases were included to assess phylogenetic relationships and perform genome analyses. Phylogenetic analysis and divergent time estimation revealed that bla NDM-1 -positive P. aeruginosa ST308 was introduced into Singapore in 2005 (95 % highest posterior density: 2001 to 2008). Core genome, resistome, and analyses of all local bla NDM-1 -positive ST308 isolates showed chromosomal integration of multiple antibiotic resistance genes (ARGs) [ aac(3)-Id , aac(6')-Il , aadA6 , aadA11 , dfrB5 , msr ( E ), floR , sul2 , and qnrVC1 ], which was absent in global bla NDM-1 -negative ST308 sequences. Most ARGs and virulence genes were conserved across isolates originating from the three different local hospitals. Close genetic relatedness of the bla NDM-1 -positive ST308 clinical and environmental isolates suggests cocirculation between the hospital environment and human hosts with the hospital environment as a potential reservoir. Core genome single nucleotide polymorphism analyses revealed possible clonal transmission of bla NDM-1 -positive ST308 isolates between the three hospitals over 7 years. Bloodstream isolates accounted for six of 95 (6.3%) clinical isolates. This study reports the introduction of a pathogenic bla NDM-1 -positive P. aeruginosa ST308 more than a decade ago in Singapore and warrants surveillance for wider dissemination. IMPORTANCE P. aeruginosa is a Gram-negative opportunistic pathogen ubiquitously found in the environment and a major cause of nosocomial infections. While the P. aeruginosa ST308 clone has been known to bear bla IMP and bla VIM among global isolates, reports of bla NDM-1 -positive P. aeruginosa ST308 are rare. The local bla NDM-1 -positive P. aeruginosa ST308 isolates detected in this study appear to be unique to this region, with evidence of chromosomal acquisition of multiple ARGs compared to global bla NDM-1 -negative P. aeruginosa ST308 isolates. Surveillance in Singapore and beyond for dissemination is essential to determine whether existing measures are sufficient to control the spread of this ST308 clone.