Microbiology and pathogenesis of Klebsiella pneumoniae infection
- Wen-Liang Yu, MD
Wen-Liang Yu, MD
- Associate Professor of Medicine
- Chi-Mei Medical Center, Taiwan
- Yin-Ching Chuang, MD
Yin-Ching Chuang, MD
- Professor of Medicine
- Chi-Mei Medical Center, Taiwan
Klebsiella pneumoniae is a gram-negative, lactose-fermenting, non-motile, aerobic rod-shaped bacterium. It has been a known human pathogen since it was first isolated in the late nineteenth century by Edwin Klebs.
The microbiology, pathogenesis, and epidemiology of infections due to K. pneumoniae will be reviewed here. The epidemiology, clinical manifestations, diagnosis, and treatment of infections due to this organism are discussed separately. (See "Clinical features, diagnosis, and treatment of Klebsiella pneumoniae infection".)
K. pneumoniae has three subspecies with homologous DNAs but different biochemical reactions: K. pneumoniae subsp pneumoniae, K. pneumoniae subsp ozaenae, and K. pneumoniae subsp rhinoscleromatis. For the remainder of this topic review, K. pneumoniae will specifically refer to K. pneumoniae subsp pneumoniae.
The following are the characteristic biochemical reactions of the different organisms:
●K. pneumoniae is lactose fermenting, H2S- and indole-negative, has a positive Voges-Proskauer (VP) reaction, is capable of growth in KCN and using citrate as a sole carbon source, and is incapable of growth at 10ºC.
- Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 1998; 11:589.
- Cryz SJ Jr, Mortimer PM, Mansfield V, Germanier R. Seroepidemiology of Klebsiella bacteremic isolates and implications for vaccine development. J Clin Microbiol 1986; 23:687.
- Fung CP, Hu BS, Chang FY, et al. A 5-year study of the seroepidemiology of Klebsiella pneumoniae: high prevalence of capsular serotype K1 in Taiwan and implication for vaccine efficacy. J Infect Dis 2000; 181:2075.
- Fung CP, Chang FY, Lee SC, et al. A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis? Gut 2002; 50:420.
- Yeh KM, Kurup A, Siu LK, et al. Capsular serotype K1 or K2, rather than magA and rmpA, is a major virulence determinant for Klebsiella pneumoniae liver abscess in Singapore and Taiwan. J Clin Microbiol 2007; 45:466.
- Fang CT, Lai SY, Yi WC, et al. Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. Clin Infect Dis 2007; 45:284.
- Chung DR, Lee SS, Lee HR, et al. Emerging invasive liver abscess caused by K1 serotype Klebsiella pneumoniae in Korea. J Infect 2007; 54:578.
- Jenney AW, Clements A, Farn JL, et al. Seroepidemiology of Klebsiella pneumoniae in an Australian Tertiary Hospital and its implications for vaccine development. J Clin Microbiol 2006; 44:102.
- Blanchette EA, Rubin SJ. Seroepidemiology of clinical isolates of Klebsiella in Connecticut. J Clin Microbiol 1980; 11:474.
- Mizuta K, Ohta M, Mori M, et al. Virulence for mice of Klebsiella strains belonging to the O1 group: relationship to their capsular (K) types. Infect Immun 1983; 40:56.
- Athamna A, Ofek I, Keisari Y, et al. Lectinophagocytosis of encapsulated Klebsiella pneumoniae mediated by surface lectins of guinea pig alveolar macrophages and human monocyte-derived macrophages. Infect Immun 1991; 59:1673.
- Ofek I, Goldhar J, Keisari Y, Sharon N. Nonopsonic phagocytosis of microorganisms. Annu Rev Microbiol 1995; 49:239.
- Kabha K, Nissimov L, Athamna A, et al. Relationships among capsular structure, phagocytosis, and mouse virulence in Klebsiella pneumoniae. Infect Immun 1995; 63:847.
- Lin JC, Chang FY, Fung CP, et al. High prevalence of phagocytic-resistant capsular serotypes of Klebsiella pneumoniae in liver abscess. Microbes Infect 2004; 6:1191.
- Sahly H, Aucken H, Benedi VJ, et al. Impairment of respiratory burst in polymorphonuclear leukocytes by extended-spectrum beta-lactamase-producing strains of Klebsiella pneumoniae. Eur J Clin Microbiol Infect Dis 2004; 23:20.
- Cortés G, Borrell N, de Astorza B, et al. Molecular analysis of the contribution of the capsular polysaccharide and the lipopolysaccharide O side chain to the virulence of Klebsiella pneumoniae in a murine model of pneumonia. Infect Immun 2002; 70:2583.
- Kawai T. Hypermucoviscosity: an extremely sticky phenotype of Klebsiella pneumoniae associated with emerging destructive tissue abscess syndrome. Clin Infect Dis 2006; 42:1359.
- Fang CT, Chuang YP, Shun CT, et al. A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J Exp Med 2004; 199:697.
- Alvarez D, Merino S, Tomás JM, et al. Capsular polysaccharide is a major complement resistance factor in lipopolysaccharide O side chain-deficient Klebsiella pneumoniae clinical isolates. Infect Immun 2000; 68:953.
- Yu WL, Ko WC, Cheng KC, et al. Association between rmpA and magA genes and clinical syndromes caused by Klebsiella pneumoniae in Taiwan. Clin Infect Dis 2006; 42:1351.
- Lee HC, Chuang YC, Yu WL, et al. Clinical implications of hypermucoviscosity phenotype in Klebsiella pneumoniae isolates: association with invasive syndrome in patients with community-acquired bacteraemia. J Intern Med 2006; 259:606.
- Nadasy KA, Domiati-Saad R, Tribble MA. Invasive Klebsiella pneumoniae syndrome in North America. Clin Infect Dis 2007; 45:e25.
- Liao PY, Chiang WC, Chen SY, et al. Rapidly fatal gas-forming pyogenic psoas abscess caused by Klebsiella pneumoniae. Clin Infect Dis 2007; 44:1253.
- Ku YH, Chuang YC, Yu WL. Clinical spectrum and molecular characteristics of Klebsiella pneumoniae causing community-acquired extrahepatic abscess. J Microbiol Immunol Infect 2008; 41:311.
- Amako K, Meno Y, Takade A. Fine structures of the capsules of Klebsiella pneumoniae and Escherichia coli K1. J Bacteriol 1988; 170:4960.
- Nassif X, Honoré N, Vasselon T, et al. Positive control of colanic acid synthesis in Escherichia coli by rmpA and rmpB, two virulence-plasmid genes of Klebsiella pneumoniae. Mol Microbiol 1989; 3:1349.
- Arakawa Y, Ohta M, Wacharotayankun R, et al. Biosynthesis of Klebsiella K2 capsular polysaccharide in Escherichia coli HB101 requires the functions of rmpA and the chromosomal cps gene cluster of the virulent strain Klebsiella pneumoniae Chedid (O1:K2). Infect Immun 1991; 59:2043.
- Nassif X, Fournier JM, Arondel J, Sansonetti PJ. Mucoid phenotype of Klebsiella pneumoniae is a plasmid-encoded virulence factor. Infect Immun 1989; 57:546.
- Wacharotayankun R, Arakawa Y, Ohta M, et al. Enhancement of extracapsular polysaccharide synthesis in Klebsiella pneumoniae by RmpA2, which shows homology to NtrC and FixJ. Infect Immun 1993; 61:3164.
- Lai YC, Peng HL, Chang HY. RmpA2, an activator of capsule biosynthesis in Klebsiella pneumoniae CG43, regulates K2 cps gene expression at the transcriptional level. J Bacteriol 2003; 185:788.
- Yu WL, Lee MF, Tang HJ, et al. Low prevalence of rmpA and high tendency of rmpA mutation correspond to low virulence of extended spectrum β-lactamase-producing Klebsiella pneumoniae isolates. Virulence 2015; 6:162.
- Struve C, Bojer M, Nielsen EM, et al. Investigation of the putative virulence gene magA in a worldwide collection of 495 Klebsiella isolates: magA is restricted to the gene cluster of Klebsiella pneumoniae capsule serotype K1. J Med Microbiol 2005; 54:1111.
- Yeh KM, Chang FY, Fung CP, et al. magA is not a specific virulence gene for Klebsiella pneumoniae strains causing liver abscess but is part of the capsular polysaccharide gene cluster of K. pneumoniae serotype K1. J Med Microbiol 2006; 55:803.
- Yeh KM, Chang FY, Fung CP, et al. Serotype K1 capsule, rather than magA per se, is really the virulence factor in Klebsiella pneumoniae strains that cause primary pyogenic liver abscess. J Infect Dis 2006; 194:403.
- 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; 193:645.
- Yu WL, Fung CP, Ko WC, et al. Polymerase chain reaction analysis for detecting capsule serotypes K1 and K2 of Klebsiella pneumoniae causing abscesses of the liver and other sites. J Infect Dis 2007; 195:1235.
- Turton JF, Englender H, Gabriel SN, et al. Genetically similar isolates of Klebsiella pneumoniae serotype K1 causing liver abscesses in three continents. J Med Microbiol 2007; 56:593.
- Yeh KM, Lin JC, Yin FY, et al. Revisiting the importance of virulence determinant magA and its surrounding genes in Klebsiella pneumoniae causing pyogenic liver abscesses: exact role in serotype K1 capsule formation. J Infect Dis 2010; 201:1259.
- Fang CT, Lai SY, Yi WC, et al. The function of wzy_K1 (magA), the serotype K1 polymerase gene in Klebsiella pneumoniae cps gene cluster. J Infect Dis 2010; 201:1268.
- Pan YJ, Fang HC, Yang HC, et al. Capsular polysaccharide synthesis regions in Klebsiella pneumoniae serotype K57 and a new capsular serotype. J Clin Microbiol 2008; 46:2231.
- Hsu CR, Lin TL, Chen YC, et al. The role of Klebsiella pneumoniae rmpA in capsular polysaccharide synthesis and virulence revisited. Microbiology 2011; 157:3446.
- Ko WC, Paterson DL, Sagnimeni AJ, et al. Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg Infect Dis 2002; 8:160.
- Tsay RW, Siu LK, Fung CP, Chang FY. Characteristics of bacteremia between community-acquired and nosocomial Klebsiella pneumoniae infection: risk factor for mortality and the impact of capsular serotypes as a herald for community-acquired infection. Arch Intern Med 2002; 162:1021.
- Wang JH, Liu YC, Lee SS, et al. Primary liver abscess due to Klebsiella pneumoniae in Taiwan. Clin Infect Dis 1998; 26:1434.
- Yang CC, Yen CH, Ho MW, Wang JH. Comparison of pyogenic liver abscess caused by non-Klebsiella pneumoniae and Klebsiella pneumoniae. J Microbiol Immunol Infect 2004; 37:176.
- Cheng DL, Liu YC, Yen MY, et al. Septic metastatic lesions of pyogenic liver abscess. Their association with Klebsiella pneumoniae bacteremia in diabetic patients. Arch Intern Med 1991; 151:1557.
- Yang CC, Chen CY, Lin XZ, et al. Pyogenic liver abscess in Taiwan: emphasis on gas-forming liver abscess in diabetics. Am J Gastroenterol 1993; 88:1911.
- Ma LC, Fang CT, Lee CZ, et al. Genomic heterogeneity in Klebsiella pneumoniae strains is associated with primary pyogenic liver abscess and metastatic infection. J Infect Dis 2005; 192:117.
- Yu WL, Ko WC, Cheng KC, et al. Comparison of prevalence of virulence factors for Klebsiella pneumoniae liver abscesses between isolates with capsular K1/K2 and non-K1/K2 serotypes. Diagn Microbiol Infect Dis 2008; 62:1.
- Lin JC, Siu LK, Fung CP, et al. Impaired phagocytosis of capsular serotypes K1 or K2 Klebsiella pneumoniae in type 2 diabetes mellitus patients with poor glycemic control. J Clin Endocrinol Metab 2006; 91:3084.
- Yu WL, Chan KS, Ko WC, et al. Lower prevalence of diabetes mellitus in patients with Klebsiella pneumoniae primary liver abscess caused by isolates of K1/K2 than with non-K1/K2 capsular serotypes. Clin Infect Dis 2007; 45:1529.
- Tomás JM, Benedí VJ, Ciurana B, Jofre J. Role of capsule and O antigen in resistance of Klebsiella pneumoniae to serum bactericidal activity. Infect Immun 1986; 54:85.
- McCallum KL, Laakso DH, Whitfield C. Use of a bacteriophage-encoded glycanase enzyme in the generation of lipopolysaccharide O side chain deficient mutants of Escherichia coli O9:K30 and Klebsiella O1:K20: role of O and K antigens in resistance to complement-mediated serum killing. Can J Microbiol 1989; 35:994.
- Albertí S, Marqués G, Camprubí S, et al. C1q binding and activation of the complement classical pathway by Klebsiella pneumoniae outer membrane proteins. Infect Immun 1993; 61:852.
- Albertí S, Alvarez D, Merino S, et al. Analysis of complement C3 deposition and degradation on Klebsiella pneumoniae. Infect Immun 1996; 64:4726.
- Shankar-Sinha S, Valencia GA, Janes BK, et al. The Klebsiella pneumoniae O antigen contributes to bacteremia and lethality during murine pneumonia. Infect Immun 2004; 72:1423.
- Miles AA, Khimji PL. Enterobacterial chelators of iron: their occurrence, detection, and relation to pathogenicity. J Med Microbiol 1975; 8:477.
- Lodge JM, Williams P, Brown MR. Influence of growth rate and iron limitation on the expression of outer membrane proteins and enterobactin by Klebsiella pneumoniae grown in continuous culture. J Bacteriol 1986; 165:353.
- Nassif X, Sansonetti PJ. Correlation of the virulence of Klebsiella pneumoniae K1 and K2 with the presence of a plasmid encoding aerobactin. Infect Immun 1986; 54:603.
- Williams P, Smith MA, Stevenson P, et al. Novel aerobactin receptor in Klebsiella pneumoniae. J Gen Microbiol 1989; 135:3173.
- Podschun R, Sievers D, Fischer A, Ullmann U. Serotypes, hemagglutinins, siderophore synthesis, and serum resistance of Klebsiella isolates causing human urinary tract infections. J Infect Dis 1993; 168:1415.
- Podschun R, Fischer A, Ullmann U. Siderophore production of Klebsiella species isolated from different sources. Zentralbl Bakteriol 1992; 276:481.
- Tarkkanen AM, Allen BL, Williams PH, et al. Fimbriation, capsulation, and iron-scavenging systems of Klebsiella strains associated with human urinary tract infection. Infect Immun 1992; 60:1187.
- Vernet V, Philippon A, Madoulet C, et al. Virulence factors (aerobactin and mucoid phenotype) in Klebsiella pneumoniae and Escherichia coli blood culture isolates. FEMS Microbiol Lett 1995; 130:51.
- Gerlach GF, Clegg S, Allen BL. Identification and characterization of the genes encoding the type 3 and type 1 fimbrial adhesins of Klebsiella pneumoniae. J Bacteriol 1989; 171:1262.
- Jones CH, Pinkner JS, Roth R, et al. FimH adhesin of type 1 pili is assembled into a fibrillar tip structure in the Enterobacteriaceae. Proc Natl Acad Sci U S A 1995; 92:2081.
- Sebghati TA, Korhonen TK, Hornick DB, Clegg S. Characterization of the type 3 fimbrial adhesins of Klebsiella strains. Infect Immun 1998; 66:2887.
- Jagnow J, Clegg S. Klebsiella pneumoniae MrkD-mediated biofilm formation on extracellular matrix- and collagen-coated surfaces. Microbiology 2003; 149:2397.
- Langstraat J, Bohse M, Clegg S. Type 3 fimbrial shaft (MrkA) of Klebsiella pneumoniae, but not the fimbrial adhesin (MrkD), facilitates biofilm formation. Infect Immun 2001; 69:5805.
- Di Martino P, Livrelli V, Sirot D, et al. A new fimbrial antigen harbored by CAZ-5/SHV-4-producing Klebsiella pneumoniae strains involved in nosocomial infections. Infect Immun 1996; 64:2266.
- Vernet V, Madoulet C, Chippaux C, Philippon A. Incidence of two virulence factors (aerobactin and mucoid phenotype) among 190 clinical isolates of Klebsiella pneumoniae producing extended-spectrum beta-lactamase. FEMS Microbiol Lett 1992; 75:1.
- Lin TL, Tang SI, Fang CT, et al. Extended-spectrum beta-lactamase genes of Klebsiella pneumoniae strains in Taiwan: recharacterization of shv-27, shv-41, and tem-116. Microb Drug Resist 2006; 12:12.
- Chan KS, Yu WL, Tsai CL, et al. Pyogenic liver abscess caused by Klebsiella pneumoniae: analysis of the clinical characteristics and outcomes of 84 patients. Chin Med J (Engl) 2007; 120:136.
- Sahly H, Aucken H, Benedí VJ, et al. Increased serum resistance in Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases. Antimicrob Agents Chemother 2004; 48:3477.