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