Coexistence of blaIMP-4 and blaSFO-1 in an IncHI5B plasmid harbored by tigecycline-non-susceptible Klebsiella variicola strain

Abstract

Background: Klebsiella variicola is considered a newly emerging human pathogen. Clinical isolates of carbapenemase and broad-spectrum β-lactamase-producing K. variicola remain relatively uncommon. A strain of K. variicola 4253 was isolated from a clinical sample, and was identified to carry the bla_IMP-4 and bla_SFO-1 genes. This study aims to discern its antibiotic resistance phenotype and genomic characteristics.

Methods: Species identification was conducted using MALDI-TOF/MS. PCR identification confirmed the presence of the bla_IMP-4 and bla_SFO-1 genes. Antibiotic resistance phenotype and genomic characteristics were detected by antimicrobial susceptibility testing and whole-genome sequencing. Plasmid characterization was carried out through S1-PFGE, conjugation experiments, Southern blot, and comparative genomic analysis.

Results: K. variicola 4253 belonged to ST347, and demonstrated resistance to broad-spectrum β-lactamase drugs and tigecycline while being insensitive to imipenem and meropenem. The bla_IMP-4 and bla_SFO-1 genes harbored on the plasmid p4253-imp. The replicon type of p4253-imp was identified as IncHI5B, representing a multidrug-resistant plasmid capable of horizontal transfer and mediating the dissemination of drug resistance. The bla_IMP-4 gene was located on the In809-like integrative element (Intl1-bla_IMP-4-aacA4-catB3), which circulates in Acinetobacter and Enterobacteriaceae.

Conclusions: This study reports the presence of a strain of K. variicola, which is insensitive to tigecycline, carrying a plasmid harboring bla_IMP-4 and bla_SFO-1. It is highly likely that the strain acquired this plasmid through horizontal transfer. The bla_IMP-4 array (Intl1-bla_IMP-4-aacA4-catB3) is also mobile in Acinetobacter and Enterobacteriaceae. So it is essential to enhance clinical awareness and conduct epidemiological surveillance on multidrug-resistant K. variicola, conjugative plasmids carrying bla_IMP-4, and the In809 integrative element.

Keywords: Klebsiella variicola; bla IMP−4; In809; IncHI5B; Tigecycline.