The role of siderophore virulence genes in the pathogenic mechanism of hypervirulent <i>Klebsiella pneumoniae</i>_West China Medical Journal

Authors：

HAN Ruihui ,  DU Yan

Department of Clinical Laboratory, the First Affiliated Hospital of Kunming Medical University / Yunnan Key Laboratory of Laboratory Medicine / Yunnan Institute of Laboratory Diagnosis, Kunming, Yunnan 650032, P. R. China;

Corresponding?author：

DU Yan, Email: duyan_m@139.com

Keywords：

Hypervirulent Klebsiella pneumoniae; Virulence genes; Siderophore

DOI：

10.7507/1002-0179.202006023

Video：

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Hypervirulent Klebsiella pneumoniae has the characteristics of high virulence and high viscosity, which can cause pneumonia, bacteremia, liver abscess, meningitis and other diseases, and in severe cases, it can be life-threatening. At present, studies on the pathogenic mechanism of hypervirulent Klebsiella pneumoniae showed that siderophore virulence genes play an important role in it. The siderophores closely related to hypervirulent Klebsiella pneumoniae virulence mainly include aerobactin, enterobactin, yersiniabactin and salmochelin. Siderophore-related virulence genes mainly include aer, iucB, iroNB and kfuBC. This article focuses on a brief review of the role of siderophore virulence genes in the pathogenic mechanism of hypervirulent Klebsiella pneumoniae, and aims to guide infection control.

Citation： HAN Ruihui, DU Yan. The role of siderophore virulence genes in the pathogenic mechanism of hypervirulent Klebsiella pneumoniae. West China Medical Journal, 2020, 35(8): 991-994. doi: 10.7507/1002-0179.202006023 Copy

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2.	Lee CR, Lee JH, Park KS, <italic>et al</italic>. Antimicrobial resistance of hypervirulent <italic>Klebsiella pneumoniae</italic>: epidemiology, hypervirulence-associated determinants, and resistance mechanisms. Front Cell Infect Microbiol, 2017, 7: 483.
3.	Guo Y, Wang S, Zhan L, <italic>et al</italic>. Microbiological and clinical characteristics of hypermucoviscous <italic>Klebsiella pneumoniae</italic> isolates associated with invasive infections in China. Front Cell Infect Microbiol, 2017, 7: 24.
4.	Rahim GR, Gupta N, Maheshwari P, <italic>et al</italic>. Monomicrobial <italic>Klebsiella pneumoniae</italic> necrotizing fasciitis: an emerging life-threatening entity. Clin Microbiol Infect, 2019, 25(3): 316-323.
5.	馬榮, 王曉丹, 聶大平. 高毒力肺炎克雷伯菌血流感染的臨床特點. 中國感染控制雜志, 2018, 17(1): 26-30.
6.	田李均, 王曉麗, 肖淑珍, 等. 醫院內高黏液性肺炎克雷伯菌的流行分布、毒力基因及臨床特征分析. 醫學版, 2017, 37(1): 43-48.
7.	Tan TY, Ong M, Cheng Y, <italic>et al</italic>. Hypermucoviscosity, rmpA, and aerobactin are associated with community-acquired <italic>Klebsiella</italic> <italic>pneumoniae</italic> bacteremic isolates causing liver abscess in Singapore. J Microbiol Immunol Infect, 2019, 52(1): 30-34.
8.	Siu LK, Yeh KM, Lin JC, <italic>et al</italic>. <italic>Klebsiella pneumoniae</italic> liver abscess: a new invasive syndrome. Lancet Infect Dis, 2012, 12(11): 881-887.
9.	Lawlor MS, O’connor C, Miller VL. Yersiniabactin is a virulence factor for <italic>Klebsiella pneumoniae </italic>during pulmonary infection. Infect Immun, 2007, 75(3): 1463-1472.
10.	張杰, 喻華. 四川省人民醫院肝膿腫患者血培養分離肺炎克雷伯桿菌鐵系統基因攜帶情況的分析. 中國循證醫學雜志, 2017, 17(8): 907-909.
11.	Miethke M, Marahiel MA. Siderophore-based iron acquisition and pathogen control. Microbiol Mol Biol Rev, 2007, 71(3): 413-451.
12.	Sandy M, Butler A. Microbial iron acquisition: marine and terrestrial siderophores. Chem Rev, 2009, 109(10): 4580-4595.
13.	Shon AS, Bajwa RP, Russo TA. Hypervirulent (hypermucoviscous)<italic> Klebsiella pneumoniae</italic>: a new and dangerous breed. Virulence, 2013, 4(2): 107-118.
14.	Fang CT, Chuang YP, Shun CT, <italic>et al</italic>. A novel virulence gene in <italic>Klebsiella pneumoniae </italic>strains causing primary liver abscess and septic metastatic complications. J Exp Med, 2004, 199(5): 697-705.
15.	Catalán-Nájera JC, Garza-Ramos U, Barrios-Camacho H. Hypervirulence and hypermucoviscosity: two different but complementary <italic>Klebsiella spp. </italic> phenotypes?. Virulence, 2017, 8(7): 1111-1123.
16.	Russo TA, Olson R, Fang CT, <italic>et al</italic>. Identification of biomarkers for differentiation of hypervirulent<italic> Klebsiella</italic> <italic>pneumoniae </italic>from classical K. pneumoniae. J Clin Microbiol, 2018, 56(9): e00776-18.
17.	葉璟, 黃金偉. 致肝膿腫高毒力肺炎克雷伯菌的表型及分子特征. 中國微生態學雜志, 2019, 31(6): 638-641, 646.
18.	陳帆, 張艷亭, 喬慧捷, 等. 肺炎克雷伯菌肝膿腫的臨床特征分析. 臨床肝膽病雜志, 2016, 32(4): 764-768.
19.	Ye M, Tu J, Jiang J, <italic>et al</italic>. Clinical and genomic analysis of liver abscess-causing <italic>Klebsiella pneumoniae </italic>identifies new liver abscess-associated virulence genes. Front Cell Infect Microbiol, 2016, 6: 165.
20.	Gu DX, Huang YL, Ma JH, <italic>et al</italic>. Detection of colistin resistance gene mcr-1 in hypervirulent <italic>Klebsiella</italic> <italic>pneumoniae </italic>and <italic>Escherichia coli</italic> isolates from an infant with diarrhea in China. Antimicrob Agents Chemother, 2016, 60(8): 5099-5100.
21.	陳潔, 邵鴻迎, 趙明, 等. 肺炎克雷伯菌毒力因子的分布特征及其對小鼠的致死性. 中國科技論文, 2015, 10(6): 659-662.
22.	Hennequin C, Robin F. Correlation between antimicrobial resistance and virulence in <italic>Klebsiella pneumoniae</italic>. Eur J Clin Microbiol Infect Dis, 2016, 35(3): 333-341.
23.	Yu WL, Ko WC, Cheng KC, <italic>et al</italic>. Comparison of prevalence of virulence factors for <italic>Klebsiella</italic> <italic>pneumoniae </italic>liver abscesses between isolates with capsular K1/K2 and non-K1/K2 serotypes. Diagn Microbiol Infect Dis, 2008, 62(1): 1-6.
24.	Davoudi-Monfared E, Khalili H. The threat of carbapenem-resistant gram-negative bacteria in a Middle East region. Infect Drug Resist, 2018, 11: 1831-1880.
25.	Lam MMC, Wick RR, Wyres KL, <italic>et al</italic>. Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in <italic>Klebsiella</italic> <italic>pneumoniae </italic>populations. Microb Genom, 2018, 4(9): e000196.
26.	Bailey DC, Alexander E, Rice MR, <italic>et al</italic>. Structural and functional delineation of aerobactin biosynthesis in hypervirulent <italic>Klebsiella pneumoniae</italic>. J Biol Chem, 2018, 293(20): 7841-7852.
27.	Paauw A, Leverstein-van Hall MA, van Kessel KP, <italic>et al</italic>. <italic>Yersiniabactin</italic> reduces the respiratory oxidative stress response of innate immune cells. PLoS One, 2009, 4(12): e8240.
28.	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.
29.	Schubert S, Picard B, Gouriou S, <italic>et al</italic>. <italic>Yersinia </italic>high-pathogenicity island contributes to virulence in <italic>Escherichia coli</italic> causing extraintestinal infections. Infect Immun, 2002, 70(9): 5335-5337.

1. Liu YC, Cheng DL, Lin CL. <italic>Klebsiella</italic> <italic>pneumoniae</italic> liver abscess associated with septic endophthalmitis. Arch Intern Med, 1986, 146(10): 1913-1916.
2. Lee CR, Lee JH, Park KS, <italic>et al</italic>. Antimicrobial resistance of hypervirulent <italic>Klebsiella pneumoniae</italic>: epidemiology, hypervirulence-associated determinants, and resistance mechanisms. Front Cell Infect Microbiol, 2017, 7: 483.
3. Guo Y, Wang S, Zhan L, <italic>et al</italic>. Microbiological and clinical characteristics of hypermucoviscous <italic>Klebsiella pneumoniae</italic> isolates associated with invasive infections in China. Front Cell Infect Microbiol, 2017, 7: 24.
4. Rahim GR, Gupta N, Maheshwari P, <italic>et al</italic>. Monomicrobial <italic>Klebsiella pneumoniae</italic> necrotizing fasciitis: an emerging life-threatening entity. Clin Microbiol Infect, 2019, 25(3): 316-323.
5. 馬榮, 王曉丹, 聶大平. 高毒力肺炎克雷伯菌血流感染的臨床特點. 中國感染控制雜志, 2018, 17(1): 26-30.
6. 田李均, 王曉麗, 肖淑珍, 等. 醫院內高黏液性肺炎克雷伯菌的流行分布、毒力基因及臨床特征分析. 醫學版, 2017, 37(1): 43-48.
7. Tan TY, Ong M, Cheng Y, <italic>et al</italic>. Hypermucoviscosity, rmpA, and aerobactin are associated with community-acquired <italic>Klebsiella</italic> <italic>pneumoniae</italic> bacteremic isolates causing liver abscess in Singapore. J Microbiol Immunol Infect, 2019, 52(1): 30-34.
8. Siu LK, Yeh KM, Lin JC, <italic>et al</italic>. <italic>Klebsiella pneumoniae</italic> liver abscess: a new invasive syndrome. Lancet Infect Dis, 2012, 12(11): 881-887.
9. Lawlor MS, O’connor C, Miller VL. Yersiniabactin is a virulence factor for <italic>Klebsiella pneumoniae </italic>during pulmonary infection. Infect Immun, 2007, 75(3): 1463-1472.
10. 張杰, 喻華. 四川省人民醫院肝膿腫患者血培養分離肺炎克雷伯桿菌鐵系統基因攜帶情況的分析. 中國循證醫學雜志, 2017, 17(8): 907-909.
11. Miethke M, Marahiel MA. Siderophore-based iron acquisition and pathogen control. Microbiol Mol Biol Rev, 2007, 71(3): 413-451.
12. Sandy M, Butler A. Microbial iron acquisition: marine and terrestrial siderophores. Chem Rev, 2009, 109(10): 4580-4595.
13. Shon AS, Bajwa RP, Russo TA. Hypervirulent (hypermucoviscous)<italic> Klebsiella pneumoniae</italic>: a new and dangerous breed. Virulence, 2013, 4(2): 107-118.
14. Fang CT, Chuang YP, Shun CT, <italic>et al</italic>. A novel virulence gene in <italic>Klebsiella pneumoniae </italic>strains causing primary liver abscess and septic metastatic complications. J Exp Med, 2004, 199(5): 697-705.
15. Catalán-Nájera JC, Garza-Ramos U, Barrios-Camacho H. Hypervirulence and hypermucoviscosity: two different but complementary <italic>Klebsiella spp. </italic> phenotypes?. Virulence, 2017, 8(7): 1111-1123.
16. Russo TA, Olson R, Fang CT, <italic>et al</italic>. Identification of biomarkers for differentiation of hypervirulent<italic> Klebsiella</italic> <italic>pneumoniae </italic>from classical K. pneumoniae. J Clin Microbiol, 2018, 56(9): e00776-18.
17. 葉璟, 黃金偉. 致肝膿腫高毒力肺炎克雷伯菌的表型及分子特征. 中國微生態學雜志, 2019, 31(6): 638-641, 646.
18. 陳帆, 張艷亭, 喬慧捷, 等. 肺炎克雷伯菌肝膿腫的臨床特征分析. 臨床肝膽病雜志, 2016, 32(4): 764-768.
19. Ye M, Tu J, Jiang J, <italic>et al</italic>. Clinical and genomic analysis of liver abscess-causing <italic>Klebsiella pneumoniae </italic>identifies new liver abscess-associated virulence genes. Front Cell Infect Microbiol, 2016, 6: 165.
20. Gu DX, Huang YL, Ma JH, <italic>et al</italic>. Detection of colistin resistance gene mcr-1 in hypervirulent <italic>Klebsiella</italic> <italic>pneumoniae </italic>and <italic>Escherichia coli</italic> isolates from an infant with diarrhea in China. Antimicrob Agents Chemother, 2016, 60(8): 5099-5100.
21. 陳潔, 邵鴻迎, 趙明, 等. 肺炎克雷伯菌毒力因子的分布特征及其對小鼠的致死性. 中國科技論文, 2015, 10(6): 659-662.
22. Hennequin C, Robin F. Correlation between antimicrobial resistance and virulence in <italic>Klebsiella pneumoniae</italic>. Eur J Clin Microbiol Infect Dis, 2016, 35(3): 333-341.
23. Yu WL, Ko WC, Cheng KC, <italic>et al</italic>. Comparison of prevalence of virulence factors for <italic>Klebsiella</italic> <italic>pneumoniae </italic>liver abscesses between isolates with capsular K1/K2 and non-K1/K2 serotypes. Diagn Microbiol Infect Dis, 2008, 62(1): 1-6.
24. Davoudi-Monfared E, Khalili H. The threat of carbapenem-resistant gram-negative bacteria in a Middle East region. Infect Drug Resist, 2018, 11: 1831-1880.
25. Lam MMC, Wick RR, Wyres KL, <italic>et al</italic>. Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in <italic>Klebsiella</italic> <italic>pneumoniae </italic>populations. Microb Genom, 2018, 4(9): e000196.
26. Bailey DC, Alexander E, Rice MR, <italic>et al</italic>. Structural and functional delineation of aerobactin biosynthesis in hypervirulent <italic>Klebsiella pneumoniae</italic>. J Biol Chem, 2018, 293(20): 7841-7852.
27. Paauw A, Leverstein-van Hall MA, van Kessel KP, <italic>et al</italic>. <italic>Yersiniabactin</italic> reduces the respiratory oxidative stress response of innate immune cells. PLoS One, 2009, 4(12): e8240.
28. 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.
29. Schubert S, Picard B, Gouriou S, <italic>et al</italic>. <italic>Yersinia </italic>high-pathogenicity island contributes to virulence in <italic>Escherichia coli</italic> causing extraintestinal infections. Infect Immun, 2002, 70(9): 5335-5337.

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The role of siderophore virulence genes in the pathogenic mechanism of hypervirulent Klebsiella pneumoniae

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