Dissemination of virulence and resistance genes among Klebsiella pneumoniae via outer membrane vesicle: An important plasmid transfer mechanism to promote the emergence of carbapenem‐resistant hypervirulent Klebsiella pneumoniae

Transboundary and Emerging DiseasesVolume 69, Issue 5 p. e2661-e2676 ORIGINAL ARTICLE Dissemination of virulence and resistance genes among Klebsiella pneumoniae via outer membrane vesicle: An important plasmid transfer mechanism to promote the emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae Zhongxing Wang, Zhongxing Wang Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, China MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaSearch for more papers by this authorZhe Wen, Zhe Wen Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, China MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaSearch for more papers by this authorMin Jiang, Min Jiang MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaSearch for more papers by this authorFufang Xia, Fufang Xia MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaSearch for more papers by this authorMin Wang, Min Wang Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, ChinaSearch for more papers by this authorXiangkai Zhuge, Corresponding Author Xiangkai Zhuge [email protected] orcid.org/0000-0002-9034-0580 Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, China MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China Correspondence Xiangkai Zhuge, Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226019, China. Email: [email protected] Jianjun Dai, Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; Address: No.1 Weigang road, Nanjing, Jiangsu Province, China.Email: [email protected]Search for more papers by this authorJianjun Dai, Corresponding Author Jianjun Dai [email protected] orcid.org/0000-0002-9123-5731 MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China College of Pharmacy, China Pharmaceutical University, Nanjing, China Correspondence Xiangkai Zhuge, Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226019, China. Email: [email protected] Jianjun Dai, Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; Address: No.1 Weigang road, Nanjing, Jiangsu Province, China.Email: [email protected]Search for more papers by this author Zhongxing Wang, Zhongxing Wang Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, China MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaSearch for more papers by this authorZhe Wen, Zhe Wen Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, China MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaSearch for more papers by this authorMin Jiang, Min Jiang MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaSearch for more papers by this authorFufang Xia, Fufang Xia MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaSearch for more papers by this authorMin Wang, Min Wang Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, ChinaSearch for more papers by this authorXiangkai Zhuge, Corresponding Author Xiangkai Zhuge [email protected] orcid.org/0000-0002-9034-0580 Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, China MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China Correspondence Xiangkai Zhuge, Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226019, China. Email: [email protected] Jianjun Dai, Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; Address: No.1 Weigang road, Nanjing, Jiangsu Province, China.Email: [email protected]Search for more papers by this authorJianjun Dai, Corresponding Author Jianjun Dai [email protected] orcid.org/0000-0002-9123-5731 MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China College of Pharmacy, China Pharmaceutical University, Nanjing, China Correspondence Xiangkai Zhuge, Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226019, China. Email: [email protected] Jianjun Dai, Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China; Address: No.1 Weigang road, Nanjing, Jiangsu Province, China.Email: [email protected]Search for more papers by this author First published: 09 June 2022 https://doi.org/10.1111/tbed.14615Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Klebsiella pneumoniae is well-known opportunistic enterobacteria involved in complex clinical infections in humans and animals. The domestic animals might be a source of the multidrug-resistant virulent K. pneumoniae to humans. K. pneumoniae infections in domestic animals are considered as an emergent global concern. The horizontal gene transfer plays essential roles in bacterial genome evolution by spread of virulence and resistance determinants. However, the virulence genes can be transferred horizontally via K. pneumoniae-derived outer membrane vesicles (OMVs) remains to be unreported. In this study, we performed complete genome sequencing of two K. pneumoniae HvK2115 and CRK3022 with hypervirulent or carbapenem-resistant traits. OMVs from K. pneumoniae HvK2115 and CRK3022 were purified and observed. The carriage of virulence or resistance genes in K. pneumoniae OMVs was identified. The influence of OMVs on the horizontal transfer of virulence-related or drug-resistant plasmids among K. pneumoniae strains was evaluated thoroughly. The plasmid transfer to recipient bacteria through OMVs was identified by polymerase chain reaction, pulsed field gel electrophoresis and Southern blot. This study revealed that OMVs could mediate the intraspecific and interspecific horizontal transfer of the virulence plasmid phvK2115. OMVs could simultaneously transfer two resistance plasmids into K. pneumoniae and Escherichia coli recipient strains. OMVs-mediated horizontal transfer of virulence plasmid phvK2115 could significantly enhance the pathogenicity of human carbapenem-resistant K. pneumoniae CRK3022. The CRK3022 acquired the virulence plasmid phvK2115 could become a CR-hvKp strain. It was critically important that OMVs-mediated horizontal transfer of phvK2115 lead to the coexistence of virulence and carbapenem-resistance genes in K. pneumoniae, resulting in the emerging of carbapenem-resistant hypervirulent K. pneumoniae. CONFLICT OF INTEREST The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article. Open Research DATA AVAILABILITY STATEMENT All data generated or analyzed during this study are included in this published article. Supporting Information Filename Description tbed14615-sup-0001-TableS1.docx26.6 KB Table S1. Bacterial strains, plasmid and oligonucleotide sequences of PCR primers used in this study. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. 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