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