High-Level Aminoglycoside Resistance in Human Clinical Klebsiella pneumoniae Complex Isolates and Characteristics of armA-Carrying IncHI5 Plasmids

Abstract

Aminoglycosides are important options for treating life-threatening infections. However, high levels of aminoglycoside resistance (HLAR) among <i>Klebsiella pneumoniae</i> isolates have been observed to be increasing frequently. In this study, a total of 292 isolates of the <i>K. pneumoniae</i> complex from a teaching hospital in China were analyzed. Among these isolates, the percentage of HLAR strains was 13.7% (40/292), and 15 aminoglycoside resistance genes were identified among the HLAR strains, with <i>rmtB</i> being the most dominant resistance gene (70%, 28/40). We also described an <i>armA</i>-carrying <i>Klebsiella variicola</i> strain KP2757 that exhibited a high-level resistance to all aminoglycosides tested. Whole-genome sequencing of KP2757 demonstrated that the strain contained one chromosome and three plasmids, with all the aminoglycoside resistance genes (including two copies of <i>armA</i> and six AME genes) being located on a conjugative plasmid, p2757-346, belonging to type IncHI5. Comparative genomic analysis of eight IncHI5 plasmids showed that six of them carried two copies of the intact <i>armA</i> gene in the complete or truncated Tn<i>1548</i> transposon. To the best of our knowledge, for the first time, we observed that two copies of <i>armA</i> together with six AME genes coexisted on the same plasmid in a strain of <i>K. variicola</i> with HLAR. Comparative genomic analysis of eight <i>armA</i>-carrying IncHI5 plasmids isolated from humans and sediment was performed, suggesting the potential for dissemination of these plasmids among bacteria from different sources. These results demonstrated the necessity of monitoring the prevalence of IncHI5 plasmids to restrict their worldwide dissemination.