Ruichao Li1, Jing Cheng2, Huiyue Dong2, Leyuan Li2, Wentian Liu2, Chunli Zhang2, Xianju Feng3, Shangshang Qin4. 1. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Institute of Comparative Medicine, Yangzhou University, Yangzhou, Jiangsu, China. 2. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China. 3. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 4. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, Henan, China. Electronic address: qinshangshang@126.com.
Abstract
INTRODUCTION: Co-existence of both virulence and multidrug-resistant (MDR) determinants on a self-transmissible plasmid facilitates simultaneous transfer of virulence and resistance in a single event and rapid emergence of virulent and MDR Klebsiella pneumoniae clones. METHOD: This study identified extensively drug-resistant ST15 strains, KP17-15 and KP17-16, from clinical cases with microbiological and genomical approaches. RESULTS: The chromosomes of KP17-15 and KP17-16 were highly homologous with 12 SNP differences, indicating that the two strains were derived from the same clone. Multiple plasmids existed in the isolates, including novel virulence plasmids p17-15-vir (479 kb) and p17-16-vir (290 kb) for KP17-15 and KP17-16, respectively. Notably, the plasmid p17-15-vir (479 kb) was a hybrid plasmid that might be formed by recombination of two homologous regions encoding group II intron reverse transcriptase and mobile element ISShes11 shared by p17-16-vir (290 kb) and a conjugative MDR plasmid p17-16-CTX (188 kb). p17-15-vir was readily transferable to ST11 Klebsiella pneumoniae by conjugation. Moreover, p17-16-vir, a non-conjugative virulence plasmid lacking the transfer (tra) operon, was also transferable by conjugation under the help of p17-16-CTX or p17-16-KPC. Fusion of p17-16-vir with p17-16-CTX into a p17-15-vir-like plasmid was also observed in the transconjugant. CONCLUSION: The findings uncover the evolutionary pathway of a novel hybrid virulence MDR plasmid and transfer mechanism of a non-conjugative virulence plasmid. Systematic surveillance of such hybrid virulence MDR plasmids in clinical Klebsiella pneumoniae should be performed.
INTRODUCTION: Co-existence of both virulence and multidrug-resistant (MDR) determinants on a self-transmissible plasmid facilitates simultaneous transfer of virulence and resistance in a single event and rapid emergence of virulent and MDR Klebsiella pneumoniae clones. METHOD: This study identified extensively drug-resistant ST15 strains, KP17-15 and KP17-16, from clinical cases with microbiological and genomical approaches. RESULTS: The chromosomes of KP17-15 and KP17-16 were highly homologous with 12 SNP differences, indicating that the two strains were derived from the same clone. Multiple plasmids existed in the isolates, including novel virulence plasmids p17-15-vir (479 kb) and p17-16-vir (290 kb) for KP17-15 and KP17-16, respectively. Notably, the plasmid p17-15-vir (479 kb) was a hybrid plasmid that might be formed by recombination of two homologous regions encoding group II intron reverse transcriptase and mobile element ISShes11 shared by p17-16-vir (290 kb) and a conjugative MDR plasmid p17-16-CTX (188 kb). p17-15-vir was readily transferable to ST11 Klebsiella pneumoniae by conjugation. Moreover, p17-16-vir, a non-conjugative virulence plasmid lacking the transfer (tra) operon, was also transferable by conjugation under the help of p17-16-CTX or p17-16-KPC. Fusion of p17-16-vir with p17-16-CTX into a p17-15-vir-like plasmid was also observed in the transconjugant. CONCLUSION: The findings uncover the evolutionary pathway of a novel hybrid virulence MDR plasmid and transfer mechanism of a non-conjugative virulence plasmid. Systematic surveillance of such hybrid virulence MDR plasmids in clinical Klebsiella pneumoniae should be performed.