Increased Resistance to Carbapenems in Proteus mirabilis Mediated by Amplification of the blaVIM-1-Carrying and IS26-Associated Class 1 Integron

Objective: The aim of the study was to decipher the mechanisms and associated genetic determinants responsible for increased carbapenem resistance among Proteus mirabilis clinical isolates. Methods: The entire genetic structure surrounding the beta-lactam resistance genes was characterized by PCR, gene walking, and DNA sequencing. Results: A series of clinical P. mirabilis isolates were consecutively recovered from different patients at the Military hospital of Sofia, Bulgaria. They showed variable levels of resistance to carbapenems. All isolates produced the same carbapenemase VIM-1 that was chromosomally encoded. We showed that increased resistance to carbapenems was related to an increased number of bla(VIM-1) gene copies. Conclusion: We showed here that increased carbapenem resistance in P. mirabilis may result from increased expression of the bla(VIM-1) carbapenemase gene through multiplication of its copy number.