Newly Detected Transmission of blaKPC-2 by Outer Membrane Vesicles in Klebsiella Pneumoniae

Abstract

Objective: The prevalence of carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a global public health problem. It is mainly caused by the plasmid-carried carbapenemase gene. Outer membrane vesicles (OMVs) contain toxins and other factors involved in various biological processes, including β-lactamase and antibiotic-resistance genes. This study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella (K.) pneumoniae.

Methods: We selected CR-KP producing K. pneumoniae carbapenemase-2 (KPC-2) to study whether they can transfer resistance genes through OMVs. The OMVs of CR-KP were obtained by ultracentrifugation, and incubated with carbapenem-sensitive K. pneumoniae for 4 h. Finally, the carbapenem-sensitive K. pneumoniae was tested for the presence of bla_KPC-2 resistance gene and its sensitivity to carbapenem antibiotics.

Results: The existence of OMVs was observed by the electron microscopy. The extracted OMVs had bla_KPC-2 resistance gene. After incubation with OMVs, bla_KPC-2 resistance gene was detected in sensitive K. pneumoniae, and it became resistant to imipenem and meropenem.

Conclusion: This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_KPC-2 to sensitive K. pneumoniae, allowing the bacteria to produce carbapenemase, which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.

Keywords: bla KPC-2; carbapenem-resistant Klebsiella pneumoniae; carbapenemase; outer membrane vesicles; simplified carbapenem inactivation method.