PER extended-spectrum β-lactamases originate from Pararheinheimera spp

To investigate the origin of PER extended-spectrum β-lactamases, publicly available sequence databases were searched for bla_PER-like genes. Three genomes from Pararheinheimera, a genus associated with water and soil environments, were found to carry bla_PER-like genes but lacked the ISCR1/ISPa12/ISPa13 insertion sequences commonly associated with bla_PER in clinical isolates. Sequence analysis revealed 78-96% nucleotide identity and conserved synteny between the clinical mobile genetic elements (MGEs) encoding bla_PER-1 and the bla_PER locus in the Pararheinheimera genomes. Notably, bla_PER genes were only identified in 3 of 21 Pararheinheimera and Rheinheimera genomes, whereas the genetic environment of bla_PER genes as found in clinical MGEs was conserved in all Pararheinheimera and Rheinheimera genomes. These findings indicate that bla_PER genes were likely acquired by a branch of the Pararheinheimera genus long before the antibiotic era. Later, bla_PER genes were mobilised, likely through the involvement of insertion sequences, from one or several Pararheinheimera species, allowing their dissemination into human pathogens.