- 1. China‐Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, P. R. China;
- 2. Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, China‐Japan Friendship Hospital, Beijing 100029, P. R. China;
Compared to classical Klebsiella pneumoniae, hypervirulent Klebsiella pneumoniae (hvKP) exhibits stronger pathogenicity and a greater ability to evade host immune responses. Infections caused by hvKP typically manifest as more severe diseases with higher mortality rates, thereby increasing the complexity and challenges of clinical treatment. The emergence of carbapenem-resistant hvKP (CR-hvKP) exacerbates this predicament. Although there is still confusion regarding the clinical definition and detection standards for hvKP, this article systematically explains the clinical infection characteristics, identification methods, and mechanisms behind the emergence of CR-hvKP. This can enhance clinical staff’s vigilance towards hvKP infections and offer comprehensive and detailed considerations for the diagnosis and treatment of such strains.
Citation: YANG Xinrui, ZHANG Feilong, LU Binghuai. Clinical infections and laboratory identification of hypervirulent Klebsiella pneumoniae: confusions and advances. West China Medical Journal, 2024, 39(8): 1173-1178. doi: 10.7507/1002-0179.202407264 Copy
1. | 中国老年医学学会检验医学分会, 上海市医学会检验医学专科分会, 上海市微生物学会临床微生物学专业委员会. 高毒力肺炎克雷伯菌实验室检测专家共识. 中华检验医学杂志, 2023, 46(11): 1164-1172. |
2. | Liu YC, Cheng DL, Lin CL. Klebsiella pneumoniae liver abscess associated with septic endophthalmitis. Arch Intern Med, 1986, 146(10): 1913-1916. |
3. | Russo TA, Marr CM. Hypervirulent Klebsiella pneumoniae. Clin Microbiol Rev, 2019, 32(3): e00001-19. |
4. | Shon AS, Bajwa RP, Russo TA. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence, 2013, 4(2): 107-118. |
5. | Gu D, Dong N, Zheng Z, et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis, 2018, 18(1): 37-46. |
6. | Cejas D, Fernández Canigia L, Rincón Cruz G, et al. First isolate of KPC-2-producing Klebsiella pneumonaie sequence type 23 from the Americas. J Clin Microbiol, 2014, 52(9): 3483-3485. |
7. | Russo TA, Olson R, Fang CT, et al. Identification of biomarkers for differentiation of hypervirulent Klebsiella pneumoniae from classical K. pneumoniae. J Clin Microbiol, 2018, 56(9): e00776-18. |
8. | Russo TA, Macdonald U, Hassan S, et al. An assessment of siderophore production, mucoviscosity, and mouse infection models for defining the virulence spectrum of hypervirulent Klebsiella pneumoniae. mSphere, 2021, 6(2): e00045-21. |
9. | Siu LK, Yeh KM, Lin JC, et al. Klebsiella pneumoniae liver abscess: a new invasive syndrome. Lancet Infect Dis, 2012, 12(11): 881-887. |
10. | Li J, Ren J, Wang W, et al. Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections. Eur J Clin Microbiol Infect Dis, 2018, 37(4): 679-689. |
11. | Longworth S, Han J. Pyogenic liver abscess. Clin Liver Dis (Hoboken), 2015, 6(2): 51-54. |
12. | Lin JC, Chang FY, Fung CP, et al. Do neutrophils play a role in establishing liver abscesses and distant metastases caused by Klebsiella pneumoniae?. PLoS One, 2010, 5(11): e15005. |
13. | Sink JR, Pasculle WA, Shah NB, et al. Disparate domains: cryptogenic invasive Klebsiella pneumoniae liver abscess syndrome. Am J Med, 2017, 130(6): 673-677. |
14. | Kim SJ, Chu ST, Lee KS, et al. Metastatic endophthalmitis and thyroid abscess complicating Klebsiella pneumoniae liver abscess. Clin Mol Hepatol, 2018, 24(1): 88-91. |
15. | 蒋璐, 王锐英, 魏双, 等. 糖尿病患者易感高毒力肺炎克雷伯菌机制的研究进展. 中华微生物学和免疫学杂志, 2024, 44(6): 560-564. |
16. | Kumabe A, Kenzaka T. String test of hypervirulent Klebsiella pneumonia. QJM, 2014, 107(12): 1053. |
17. | Lin YC, Lu MC, Tang HL, et al. Assessment of hypermucoviscosity as a virulence factor for experimental Klebsiella pneumoniae infections: comparative virulence analysis with hypermucoviscosity-negative strain. BMC Microbiol, 2011, 11: 50. |
18. | Lee CH, Liu JW, Su LH, et al. Hypermucoviscosity associated with Klebsiella pneumoniae-mediated invasive syndrome: a prospective cross-sectional study in Taiwan. Int J Infect Dis, 2010, 14(8): e688-e692. |
19. | Walker KA, Miller VL. The intersection of capsule gene expression, hypermucoviscosity and hypervirulence in Klebsiella pneumoniae. Curr Opin Microbiol, 2020, 54: 95-102. |
20. | Eger E, Heiden SE, Becker K, et al. Hypervirulent Klebsiella pneumonia sequence type 420 with a chromosomally inserted virulence plasmid. Int J Mol Sci, 2021, 22(17): 9196. |
21. | Walker KA, Miner TA, Palacios M, et al. A Klebsiella pneumoniae regulatory mutant has reduced capsule expression but retains hypermucoviscosity. mBio, 2019, 10(2): e00089-19. |
22. | Russo TA, Olson R, MacDonald U, et al. Aerobactin, but not yersiniabactin, salmochelin, or enterobactin, enables the growth/survival of hypervirulent (hypermucoviscous) Klebsiella pneumoniae ex vivo and in vivo. Infect Immun, 2015, 83(8): 3325-3333. |
23. | Russo TA, MacDonald U. The galleria mellonella infection model does not accurately differentiate between hypervirulent and classical Klebsiella pneumoniae. mSphere, 2020, 5(1): e00850-19. |
24. | Ko KS. The contribution of capsule polysaccharide genes to virulence of Klebsiella pneumoniae. Virulence, 2017, 8(5): 485-486. |
25. | Pan YJ, Lin TL, Hsu CR, et al. Use of a Dictyostelium model for isolation of genetic loci associated with phagocytosis and virulence in Klebsiella pneumoniae. Infect Immun, 2011, 79(3): 997-1006. |
26. | March C, Cano V, Moranta D, et al. Role of bacterial surface structures on the interaction of Klebsiella pneumoniae with phagocytes. PLoS One, 2013, 8(2): e56847. |
27. | Palacios M, Miner TA, Frederick DR, et al. Identification of two regulators of virulence that are conserved in Klebsiella pneumonia classical and hypervirulent strains. mBio, 2018, 9(4): e01443-18. |
28. | Lee CR, Lee JH, Park KS, et al. Antimicrobial resistance of hypervirulent Klebsiella pneumoniae: epidemiology, hypervirulence-associated determinants, and resistance mechanisms. Front Cell Infect Microbiol, 2017, 7: 483. |
29. | Chuang YP, Fang CT, Lai SY, et al. Genetic determinants of capsular serotype K1 of Klebsiella pneumoniae causing primary pyogenic liver abscess. J Infect Dis, 2006, 193(5): 645-654. |
30. | Bullen JJ, Rogers HJ, Griffiths E. Iron binding proteins and infection. Br J Haematol, 1972, 23(4): 389-392. |
31. | Palmer LD, Skaar EP. Transition metals and virulence in bacteria. Annu Rev Genet, 2016, 50: 67-91. |
32. | Bachman MA, Oyler JE, Burns SH, et al. Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2. Infect Immun, 2011, 79(8): 3309-3316. |
33. | Hsieh PF, Lin TL, Lee CZ, et al. Serum-induced iron-acquisition systems and TonB contribute to virulence in Klebsiella pneumoniae causing primary pyogenic liver abscess. J Infect Dis, 2008, 197(12): 1717-1727. |
34. | Lawlor MS, O’Connor C, Miller VL. Yersiniabactin is a virulence factor for Klebsiella pneumoniae during pulmonary infection. Infect Immun, 2007, 75(3): 1463-1472. |
35. | Russo TA, Olson R, MacDonald U, et al. Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae. Infect Immun, 2014, 82(6): 2356-2367. |
36. | Hantke K, Nicholson G, Rabsch W, et al. Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN. Proc Natl Acad Sci U S A, 2003, 100(7): 3677-3682. |
37. | Bachman MA, Miller VL, Weiser JN. Mucosal lipocalin 2 has pro-inflammatory and iron-sequestering effects in response to bacterial enterobactin. PLoS Pathog, 2009, 5(10): e1000622. |
38. | Troxell B, Hassan HM. Transcriptional regulation by ferric uptake regulator (Fur) in pathogenic bacteria. Front Cell Infect Microbiol, 2013, 3: 59. |
39. | Lee JW, Helmann JD. Functional specialization within the Fur family of metalloregulators. Biometals, 2007, 20(3/4): 485-499. |
40. | Lin CT, Wu CC, Chen YS, et al. Fur regulation of the capsular polysaccharide biosynthesis and iron-acquisition systems in Klebsiella pneumoniae CG43. Microbiology (Reading), 2011, 15(Pt 2): 419-429. |
41. | Wyres KL, Lam MMC, Holt KE. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol, 2020, 18(6): 344-359. |
42. | Bulger J, MacDonald U, Olson R, et al. Metabolite transporter PEG344 is required for full virulence of hypervirulent klebsiella pneumoniae strain hvKP1 after pulmonary but not subcutaneous challenge. Infect Immun, 2017, 85(10): e00093-17. |
43. | Nougayrède JP, Homburg S, Taieb F, et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science, 2006, 313(5788): 848-854. |
44. | Lai YC, Lin AC, Chiang MK, et al. Genotoxic Klebsiella pneumoniae in Taiwan. PLoS One, 2014, 9(5): e96292. |
45. | Cuevas-Ramos G, Petit CR, Marcq I, et al. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci U S A, 2010, 107(25): 11537-11542. |
46. | Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis, 2009, 9(4): 228-236. |
47. | Heiden SE, Hübner NO, Bohnert JA, et al. A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition. Genome Med, 2020, 12(1): 113. |
48. | Yang X, Dong N, Chan EW, et al. Carbapenem resistance-encoding and virulence-encoding conjugative plasmids in Klebsiella pneumoniae. Trends Microbiol, 2021, 29(1): 65-83. |
49. | Navon-Venezia S, Kondratyeva K, Carattoli A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev, 2017, 41(3): 252-275. |
50. | Qi Y, Wei Z, Li L, et al. Detection of a common plasmid carrying blaKPC-2 in Enterobacteriaceae isolates from distinct cities in China. Microb Drug Resist, 2010, 16(4): 297-301. |
51. | Liu Z, Gu Y, Li X, et al. Identification and characterization of NDM-1-producing hypervirulent (hypermucoviscous) Klebsiella pneumoniae in China. Ann Lab Med, 2019, 39(2): 167-175. |
52. | Lan P, Jiang Y, Zhou J, et al. A global perspective on the convergence of hypervirulence and carbapenem resistance in Klebsiella pneumoniae. J Glob Antimicrob Resist, 2021, 25: 26-34. |
53. | Zhang Y, Jin L, Ouyang P, et al. Evolution of hypervirulence in carbapenem-resistant Klebsiella pneumoniae in China: a multicentre, molecular epidemiological analysis. J Antimicrob Chemother, 2020, 75(2): 327-336. |
54. | Dong N, Lin D, Zhang R, et al. Carriage of blaKPC-2 by a virulence plasmid in hypervirulent Klebsiella pneumoniae. J Antimicrob Chemother, 2018, 73(12): 3317-3321. |
55. | Jin L, Wang R, Gao H, et al. Identification of a novel hybrid plasmid encoding KPC-2 and virulence factors in Klebsiella pneumoniae sequence type 11. Antimicrob Agents Chemother, 2021, 65(6): e02435-20. |
56. | Wong JJ, Lu J, Edwards RA, et al. Structural basis of cooperative DNA recognition by the plasmid conjugation factor, TraM. Nucleic Acids Res, 2011, 39(15): 6775-6788. |
57. | Ramsay JP, Firth N. Diverse mobilization strategies facilitate transfer of non-conjugative mobile genetic elements. Curr Opin Microbiol, 2017, 38: 1-9. |
58. | Li X, Xie Y, Liu M, et al. oriTfinder: a web-based tool for the identification of origin of transfers in DNA sequences of bacterial mobile genetic elements. Nucleic Acids Res, 2018, 46(W1): W229-W234. |
59. | Xu Y, Zhang J, Wang M, et al. Mobilization of the nonconjugative virulence plasmid from hypervirulent Klebsiella pneumoniae. Genome Med, 2021, 13(1): 119. |
60. | Li R, Cheng J, Dong H, et al. Emergence of a novel conjugative hybrid virulence multidrug-resistant plasmid in extensively drug-resistant Klebsiella pneumoniae ST15. Int J Antimicrob Agents, 2020, 55(6): 105952. |
61. | Wyres KL, Wick RR, Judd LM, et al. Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae. PLoS Genet, 2019, 15(4): e1008114. |
62. | Anthony KG, Sherburne C, Sherburne R, et al. The role of the pilus in recipient cell recognition during bacterial conjugation mediated by F-like plasmids. Mol Microbiol, 1994, 13(6): 939-953. |
63. | Pérez-Mendoza D, de la Cruz F. Escherichia coli genes affecting recipient ability in plasmid conjugation: are there any?. BMC Genomics, 2009, 10: 71. |
64. | Tian D, Liu X, Chen W, et al. Prevalence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae under divergent evolutionary patterns. Emerg Microbes Infect, 2022, 11(1): 1936-1949. |
- 1. 中国老年医学学会检验医学分会, 上海市医学会检验医学专科分会, 上海市微生物学会临床微生物学专业委员会. 高毒力肺炎克雷伯菌实验室检测专家共识. 中华检验医学杂志, 2023, 46(11): 1164-1172.
- 2. Liu YC, Cheng DL, Lin CL. Klebsiella pneumoniae liver abscess associated with septic endophthalmitis. Arch Intern Med, 1986, 146(10): 1913-1916.
- 3. Russo TA, Marr CM. Hypervirulent Klebsiella pneumoniae. Clin Microbiol Rev, 2019, 32(3): e00001-19.
- 4. Shon AS, Bajwa RP, Russo TA. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence, 2013, 4(2): 107-118.
- 5. Gu D, Dong N, Zheng Z, et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis, 2018, 18(1): 37-46.
- 6. Cejas D, Fernández Canigia L, Rincón Cruz G, et al. First isolate of KPC-2-producing Klebsiella pneumonaie sequence type 23 from the Americas. J Clin Microbiol, 2014, 52(9): 3483-3485.
- 7. Russo TA, Olson R, Fang CT, et al. Identification of biomarkers for differentiation of hypervirulent Klebsiella pneumoniae from classical K. pneumoniae. J Clin Microbiol, 2018, 56(9): e00776-18.
- 8. Russo TA, Macdonald U, Hassan S, et al. An assessment of siderophore production, mucoviscosity, and mouse infection models for defining the virulence spectrum of hypervirulent Klebsiella pneumoniae. mSphere, 2021, 6(2): e00045-21.
- 9. Siu LK, Yeh KM, Lin JC, et al. Klebsiella pneumoniae liver abscess: a new invasive syndrome. Lancet Infect Dis, 2012, 12(11): 881-887.
- 10. Li J, Ren J, Wang W, et al. Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections. Eur J Clin Microbiol Infect Dis, 2018, 37(4): 679-689.
- 11. Longworth S, Han J. Pyogenic liver abscess. Clin Liver Dis (Hoboken), 2015, 6(2): 51-54.
- 12. Lin JC, Chang FY, Fung CP, et al. Do neutrophils play a role in establishing liver abscesses and distant metastases caused by Klebsiella pneumoniae?. PLoS One, 2010, 5(11): e15005.
- 13. Sink JR, Pasculle WA, Shah NB, et al. Disparate domains: cryptogenic invasive Klebsiella pneumoniae liver abscess syndrome. Am J Med, 2017, 130(6): 673-677.
- 14. Kim SJ, Chu ST, Lee KS, et al. Metastatic endophthalmitis and thyroid abscess complicating Klebsiella pneumoniae liver abscess. Clin Mol Hepatol, 2018, 24(1): 88-91.
- 15. 蒋璐, 王锐英, 魏双, 等. 糖尿病患者易感高毒力肺炎克雷伯菌机制的研究进展. 中华微生物学和免疫学杂志, 2024, 44(6): 560-564.
- 16. Kumabe A, Kenzaka T. String test of hypervirulent Klebsiella pneumonia. QJM, 2014, 107(12): 1053.
- 17. Lin YC, Lu MC, Tang HL, et al. Assessment of hypermucoviscosity as a virulence factor for experimental Klebsiella pneumoniae infections: comparative virulence analysis with hypermucoviscosity-negative strain. BMC Microbiol, 2011, 11: 50.
- 18. Lee CH, Liu JW, Su LH, et al. Hypermucoviscosity associated with Klebsiella pneumoniae-mediated invasive syndrome: a prospective cross-sectional study in Taiwan. Int J Infect Dis, 2010, 14(8): e688-e692.
- 19. Walker KA, Miller VL. The intersection of capsule gene expression, hypermucoviscosity and hypervirulence in Klebsiella pneumoniae. Curr Opin Microbiol, 2020, 54: 95-102.
- 20. Eger E, Heiden SE, Becker K, et al. Hypervirulent Klebsiella pneumonia sequence type 420 with a chromosomally inserted virulence plasmid. Int J Mol Sci, 2021, 22(17): 9196.
- 21. Walker KA, Miner TA, Palacios M, et al. A Klebsiella pneumoniae regulatory mutant has reduced capsule expression but retains hypermucoviscosity. mBio, 2019, 10(2): e00089-19.
- 22. Russo TA, Olson R, MacDonald U, et al. Aerobactin, but not yersiniabactin, salmochelin, or enterobactin, enables the growth/survival of hypervirulent (hypermucoviscous) Klebsiella pneumoniae ex vivo and in vivo. Infect Immun, 2015, 83(8): 3325-3333.
- 23. Russo TA, MacDonald U. The galleria mellonella infection model does not accurately differentiate between hypervirulent and classical Klebsiella pneumoniae. mSphere, 2020, 5(1): e00850-19.
- 24. Ko KS. The contribution of capsule polysaccharide genes to virulence of Klebsiella pneumoniae. Virulence, 2017, 8(5): 485-486.
- 25. Pan YJ, Lin TL, Hsu CR, et al. Use of a Dictyostelium model for isolation of genetic loci associated with phagocytosis and virulence in Klebsiella pneumoniae. Infect Immun, 2011, 79(3): 997-1006.
- 26. March C, Cano V, Moranta D, et al. Role of bacterial surface structures on the interaction of Klebsiella pneumoniae with phagocytes. PLoS One, 2013, 8(2): e56847.
- 27. Palacios M, Miner TA, Frederick DR, et al. Identification of two regulators of virulence that are conserved in Klebsiella pneumonia classical and hypervirulent strains. mBio, 2018, 9(4): e01443-18.
- 28. Lee CR, Lee JH, Park KS, et al. Antimicrobial resistance of hypervirulent Klebsiella pneumoniae: epidemiology, hypervirulence-associated determinants, and resistance mechanisms. Front Cell Infect Microbiol, 2017, 7: 483.
- 29. Chuang YP, Fang CT, Lai SY, et al. Genetic determinants of capsular serotype K1 of Klebsiella pneumoniae causing primary pyogenic liver abscess. J Infect Dis, 2006, 193(5): 645-654.
- 30. Bullen JJ, Rogers HJ, Griffiths E. Iron binding proteins and infection. Br J Haematol, 1972, 23(4): 389-392.
- 31. Palmer LD, Skaar EP. Transition metals and virulence in bacteria. Annu Rev Genet, 2016, 50: 67-91.
- 32. Bachman MA, Oyler JE, Burns SH, et al. Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2. Infect Immun, 2011, 79(8): 3309-3316.
- 33. Hsieh PF, Lin TL, Lee CZ, et al. Serum-induced iron-acquisition systems and TonB contribute to virulence in Klebsiella pneumoniae causing primary pyogenic liver abscess. J Infect Dis, 2008, 197(12): 1717-1727.
- 34. Lawlor MS, O’Connor C, Miller VL. Yersiniabactin is a virulence factor for Klebsiella pneumoniae during pulmonary infection. Infect Immun, 2007, 75(3): 1463-1472.
- 35. Russo TA, Olson R, MacDonald U, et al. Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae. Infect Immun, 2014, 82(6): 2356-2367.
- 36. Hantke K, Nicholson G, Rabsch W, et al. Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN. Proc Natl Acad Sci U S A, 2003, 100(7): 3677-3682.
- 37. Bachman MA, Miller VL, Weiser JN. Mucosal lipocalin 2 has pro-inflammatory and iron-sequestering effects in response to bacterial enterobactin. PLoS Pathog, 2009, 5(10): e1000622.
- 38. Troxell B, Hassan HM. Transcriptional regulation by ferric uptake regulator (Fur) in pathogenic bacteria. Front Cell Infect Microbiol, 2013, 3: 59.
- 39. Lee JW, Helmann JD. Functional specialization within the Fur family of metalloregulators. Biometals, 2007, 20(3/4): 485-499.
- 40. Lin CT, Wu CC, Chen YS, et al. Fur regulation of the capsular polysaccharide biosynthesis and iron-acquisition systems in Klebsiella pneumoniae CG43. Microbiology (Reading), 2011, 15(Pt 2): 419-429.
- 41. Wyres KL, Lam MMC, Holt KE. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol, 2020, 18(6): 344-359.
- 42. Bulger J, MacDonald U, Olson R, et al. Metabolite transporter PEG344 is required for full virulence of hypervirulent klebsiella pneumoniae strain hvKP1 after pulmonary but not subcutaneous challenge. Infect Immun, 2017, 85(10): e00093-17.
- 43. Nougayrède JP, Homburg S, Taieb F, et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science, 2006, 313(5788): 848-854.
- 44. Lai YC, Lin AC, Chiang MK, et al. Genotoxic Klebsiella pneumoniae in Taiwan. PLoS One, 2014, 9(5): e96292.
- 45. Cuevas-Ramos G, Petit CR, Marcq I, et al. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci U S A, 2010, 107(25): 11537-11542.
- 46. Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis, 2009, 9(4): 228-236.
- 47. Heiden SE, Hübner NO, Bohnert JA, et al. A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition. Genome Med, 2020, 12(1): 113.
- 48. Yang X, Dong N, Chan EW, et al. Carbapenem resistance-encoding and virulence-encoding conjugative plasmids in Klebsiella pneumoniae. Trends Microbiol, 2021, 29(1): 65-83.
- 49. Navon-Venezia S, Kondratyeva K, Carattoli A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev, 2017, 41(3): 252-275.
- 50. Qi Y, Wei Z, Li L, et al. Detection of a common plasmid carrying blaKPC-2 in Enterobacteriaceae isolates from distinct cities in China. Microb Drug Resist, 2010, 16(4): 297-301.
- 51. Liu Z, Gu Y, Li X, et al. Identification and characterization of NDM-1-producing hypervirulent (hypermucoviscous) Klebsiella pneumoniae in China. Ann Lab Med, 2019, 39(2): 167-175.
- 52. Lan P, Jiang Y, Zhou J, et al. A global perspective on the convergence of hypervirulence and carbapenem resistance in Klebsiella pneumoniae. J Glob Antimicrob Resist, 2021, 25: 26-34.
- 53. Zhang Y, Jin L, Ouyang P, et al. Evolution of hypervirulence in carbapenem-resistant Klebsiella pneumoniae in China: a multicentre, molecular epidemiological analysis. J Antimicrob Chemother, 2020, 75(2): 327-336.
- 54. Dong N, Lin D, Zhang R, et al. Carriage of blaKPC-2 by a virulence plasmid in hypervirulent Klebsiella pneumoniae. J Antimicrob Chemother, 2018, 73(12): 3317-3321.
- 55. Jin L, Wang R, Gao H, et al. Identification of a novel hybrid plasmid encoding KPC-2 and virulence factors in Klebsiella pneumoniae sequence type 11. Antimicrob Agents Chemother, 2021, 65(6): e02435-20.
- 56. Wong JJ, Lu J, Edwards RA, et al. Structural basis of cooperative DNA recognition by the plasmid conjugation factor, TraM. Nucleic Acids Res, 2011, 39(15): 6775-6788.
- 57. Ramsay JP, Firth N. Diverse mobilization strategies facilitate transfer of non-conjugative mobile genetic elements. Curr Opin Microbiol, 2017, 38: 1-9.
- 58. Li X, Xie Y, Liu M, et al. oriTfinder: a web-based tool for the identification of origin of transfers in DNA sequences of bacterial mobile genetic elements. Nucleic Acids Res, 2018, 46(W1): W229-W234.
- 59. Xu Y, Zhang J, Wang M, et al. Mobilization of the nonconjugative virulence plasmid from hypervirulent Klebsiella pneumoniae. Genome Med, 2021, 13(1): 119.
- 60. Li R, Cheng J, Dong H, et al. Emergence of a novel conjugative hybrid virulence multidrug-resistant plasmid in extensively drug-resistant Klebsiella pneumoniae ST15. Int J Antimicrob Agents, 2020, 55(6): 105952.
- 61. Wyres KL, Wick RR, Judd LM, et al. Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae. PLoS Genet, 2019, 15(4): e1008114.
- 62. Anthony KG, Sherburne C, Sherburne R, et al. The role of the pilus in recipient cell recognition during bacterial conjugation mediated by F-like plasmids. Mol Microbiol, 1994, 13(6): 939-953.
- 63. Pérez-Mendoza D, de la Cruz F. Escherichia coli genes affecting recipient ability in plasmid conjugation: are there any?. BMC Genomics, 2009, 10: 71.
- 64. Tian D, Liu X, Chen W, et al. Prevalence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae under divergent evolutionary patterns. Emerg Microbes Infect, 2022, 11(1): 1936-1949.