Worldwide distribution and environmental origin of the Adelaide imipenemase (AIM-1), a potent carbapenemase in Pseudomonas aeruginosa

Abstract

Carbapenems are potent broad-spectrum β-lactam antibiotics reserved for the treatment of serious infections caused by multidrug-resistant bacteria such as <i>Pseudomonas aeruginosa</i>. The surge in <i>P. aeruginosa</i> resistant to carbapenems is an urgent threat, as very few treatment options remain. Resistance to carbapenems is predominantly due to the presence of carbapenemase enzymes. The assessment of 147 <i>P</i>. <i>aeruginosa</i> isolates revealed that 32 isolates were carbapenem non-wild-type. These isolates were screened for carbapenem resistance genes using PCR. One isolate from wastewater contained the Adelaide imipenemase gene (<i>bla</i>_AIM-1) and was compared phenotypically with a highly carbapenem-resistant clinical isolate containing the <i>bla</i>_AIM-1 gene. A further investigation of wastewater samples from various local healthcare and non-healthcare sources as well as river water, using probe-based qPCR, revealed the presence of the <i>bla</i>_AIM-1 gene in all the samples analysed. The widespread occurrence of <i>bla</i>_AIM-1 throughout Adelaide hinted at the possibility of more generally extensive spread of this gene than originally thought. A blast search revealed the presence of the <i>bla</i>_AIM-1 gene in Asia, North America and Europe. To elucidate the identity of the organism(s) carrying the <i>bla</i>_AIM-1 gene, shotgun metagenomic sequencing was conducted on three wastewater samples from different locations. Comparison of these nucleotide sequences with a whole-genome sequence of a <i>P. aeruginosa</i> isolate revealed that, unlike the genetic environment and arrangement in <i>P. aeruginosa</i>, the <i>bla</i>_AIM-1 gene was not carried as part of any mobile genetic elements. A phylogenetic tree constructed with the deduced amino acid sequences of AIM-1 suggested that the potential origin of the <i>bla</i>_AIM-1 gene in <i>P. aeruginosa</i> might be the non-pathogenic environmental organism, <i>Pseudoxanthomonas mexicana</i>.