Klebsiella pneumoniae

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A Microbial Biorealm page on the genus Klebsiella pneumoniae

Luria Agar plate streaked with K. pneumoniae. From American Society for Microbiology

Classification

Higher order taxa

Domain: Bacteria;

Phylum: Proteobacteria;

Class: Gammaproteobacteria;

Order: Enterobacteriales;

Family: Enterobacteriaceae;

Genus: Klebsiella;

Species: K. pneumoniae

NCBI: Taxonomy

Species

Klebsiella pneumoniae

NCBI: Complete genome here

Description and significance

K. pneumoniae is a gram negative bacterium. It is facultative anaerobic. It is rod-shaped and measures 2 µm by 0.5 µm. In 1882, Friedlander C. Uber first discovered Klebsiella to be a pathogen that caused pneumonia (8). Many hospital cases around the world have been linked to K. pneumoniae. Therefore, more studies of the strains were important and performed. The bacterium was isolated and sequenced from a patient in 2004. K. pneumoniae is commonly found in the gastrointestinal tract and hands of hospital personnel (3). The reason for its pathogenicity is the thick capsule layer surrounding the bacterium. It is 160 nm thick of fine fibers that protrudes out from the outer membrane at right angles (6) (5). Another site on the human body that this bacteria can be found is the nasopharynx. Its habitat is not limited to humans but is ubiquitous to the ecological environment. This includes surface water, sewage, and soil (4).

Genome structure

The complete genome was determined in 2006 at the Genome Sequencing Center at Washington University in St. Louis. The genome was named Klebsiella pneumoniae subsp. pneumoniae MGH 78578. It includes one chromosome of 5.3 Mbp. The GC content is 57%. There are five plasmids, pKPN3, pKPN4, pKPN5, pKPN6, and pKPN7. Respectively, each plasmid length is 0.18 Mbp, 0.11 Mbp, 0.089 Mbp, 0.0043 Mbp, and 0.0035 Mbp. The DNA is circular. The sequence of K. pneumoniae genome was found to be closely related that of Escherichia coli K-12 (1).

Cell structure and metabolism

Cell Structure:

K. pneumoniae contains a capsule around its cell. Known as K antigen, it is to protect the bacteria from phagocytosis. "K. pneumoniae strains of serotypes 01:Kl, 01:K10, and O1:K16, which have only the K antigen exposed at the cell surface, resist complement-mediated killing by impeding complement activation. It is also clear that purified capsular polysaccharides (K antigen) from nine different serotypes (able or unable to mask the LPS) were unable to activate complement (19)." In 1992, K. pneumoniae could be determined apart from other species of Klebsiella. Two oligonucleotide probes and the hydroxylated fatty acid C14:0-2OH are distinctive of K. pneumoniae (2).

Metabolism:

Nitrogen fixation (nif) is unique to K. penumoniae. Enterobacteriaceae don't have the characteristic of nitrogen fixation. But, K. pneumoniae can take atmospheric nitrogen gas and reduce it to ammonia and amino acids. This was discovered by analysis of hisD-linked nif genes and hisD-unlinked nif genes (9). It was later found that the structural gene for glutamine synthetase (G.S.), glnA, and a closely related glnG regulates the nif genes for nitrogenase (10). Another metabolic product of K. pneumoniae is 1,3-propanediol. It is created by anaerobic fermentation (a two-step fermentation from glucose to glycerol to 1,3-propanediol) or mild aerobic fermentation (11).

Ecology

K. pneumoniae is ubiquitous as it is found in mammals and ecological environment. It has pathogenic effects worldwide. There is evidence of community-acquired and hospital-acquired infections in countries such as Taiwan and South Africa. Community-acquired K. pneumoniae has been found, in some places, to be associated with alcoholism. There are a large number of infections acquired when it affects different organs of the body. It can affect the liver, urinary tract, lungs, to name a few (18).

Pathology

Pneumonia caused by K. pneumoniae. From Brown Medical School

K. pneumoniae is an important cause of human infections (Also see Description and significance). Infections or diseases are usually nosocomial or hospital-acquired. In 1998, K. pneumoniae and K. oxytoca accounted for 8% of nosocomial bacterial infections in the United States and in Europe. Diseases include urinary tract infections, pneumonia, septicemias, and soft tissue infections (3). The diseases caused by K. pneumoniae can result in death for patients who are immunodeficient. Differences in the diseases are determined by the different virulence factors. For example, mucoid phenotype varies as the strains for mucoid vary (14). CPS and LPS O side chain are two of the most important virulence factors of K. pneumoniae (7). They serve to protect the bacterium from phagocytosis by the host. Treatment is done by antibiotics such as clinafloxacin (13). But, there are an increasing amount of antibiotic-resistance strains. Ciprofloxacin is an antibiotic that is becoming less effective (12).

In California sea lions (Zalophus californianus) an isolate of the phenotypic characteristic hypermucoviscosity (HMV) of the bacteria Klebsiella pneumoniae has been found in a total of 25 cases. The HMV phenotype of K. pneumoniae was isolated from cases in which the sea lions had suppurative pneumonia and pleuritis; as well it was isolated from sea lions with abscesses. This is the first incidence of a pathogen that could be transmitted from marine animals to humans. Therefore, it is of great importance that marine mammals should be screened for pathogenic bacteria that could cause health problems in humans. Furthermore, K. pneumoniae HMV is starting to become more prevalent in marine coastal mammals as the primary pathogen. As a result, further studies of K. pneumoniae HMV are required to further improve and determine the extent of our understanding of this pathogen and its effects on epidemiology.(21).

Current Research

(1) Currently, Steven Clegg PhD at the University of Iowa is conducting a research of identifying regulation of genes that encode for fimbriae of enteric bacteria. K. pneumoniae is being used by taking the genes that encode for fimbriae and inserting it into and E. coli plasmid. Since E. coli fimbriae can adhere to mucosal surfaces of eukaryotes, investigation can be conducted of the regulation of expression, proteins, and amino acids. Understanding the growth of K. pneumoniae on eukaryotes or mucosal surface will enlighten the way of understanding biofilms of this bacterium inside of the human body. Infections and prevention of those infections can be determined as well (15).

Mucoid phenotype of K. pneumoniae. From Centers for Disease Control and Prevention

(2) An outbreak of IMP-1 β-lactamase-producing Klebsiella pneumoniae occurred in Japan hospitals and was acquired for investigation. Enteric bacteria have evolved a metallo-β-lactamase (MBL) resistance. The bacteria were once susceptible to β-lactam antibiotics except penicillins, but now developed resistance to expanded-spectrum β-lactams, because of extended-spectrum β-lactamases (ESBLs). Tests were done on antibiotics to determine the resistant and susceptible ones. All species are resistant to β-lactams including carbapenems such as imipenem and meropenem. The ones susceptible are those that make MBL. Patients with the bacteria at the hospital would be given levofloxacin antibiotic of the imipenem-resistant strain. It resulted in susceptibility. However, MBL-producing K. pneumoniae infections in this hospital were caused by a device-related or healthcare-associated infection. What is concluded so far is the list of sensitive drug against IMP-1 β-lactamase-producing Klebsiellan pneumoniae. Its isolation led to the solution of proper handling at the hospital because infections are derived from growth on hospital devices during patient care (16).

(3) Since the number of effective antibiotics is declining, scientists have measured the effectiveness of anti-virulence molecules on K. pneumoniae. This molecule is antibacterial; it doesn't prevent growth in vitro but prevents biosynthesis of the Klebsiella capsule and lipopolysaccharides, a the two important virulence factors. D1 and D41 (related triazines) and D0 (inactive triazine) measured their minimal inhibitory concentration. Growth on either D1 or D41 but not on D0 identified the extent of conservation of the virulence molecule. Further tests can be done and extended to human use in order to find a alternative in anti-virulence if antibiotics don't work (17).

(4) A study was conducted in a Jamaican hospital over a 5 year period that led to the conclusion that K. pneumoniae showed endemic persistence of select clones. This led to the prediction that this organism is transferred from patients to patients and from health care workers to patients. (20).

References

(1) McClelland, M., Florea, L., Sanderson, K., Clifton, S., Parkhill, J., Churcher, C., Dougan, G., Wilson, R., Miller, W. "Comparison of the Escherichia coli K-12 genome with sampled genomes of a Klebsiella pneumoniae and three Salmonella enterica serovars, Typhimurium, Typhi and Paratyphi". Nucleic Acids Res.. 2000. Volume 28(24). p. 4974–4986.

(2) Spierings, G., van Silfhout, A., Hofstra, H., and Tommassen, J. "Identification of Klebsiella pneumoniae by DNA hybridization and fatty acid analysis". International Journal of Systematic Bacteriology. 1992. Volume 42. p. 252-256.

(3) Podschun, R. and Ullmann U. "Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors". Clinical Microbiology Reviews. 1998. Volume 11, No. 4. p. 589-603.

(4) Brisse, S. and Verhoef, J. "Phylogenetic diversity of Klebsiella pneumoniae and Klebsiella oxytoca clinical isolates revealed by randomly amplified polymorphic DNA, gyrA and parC genes sequencing and automated ribotyping". International Journal of Systematic and Evolutionary Microbiology. 2001. Volume 51. p. 915–924.

(5) Lawlor, M., Hsu, J., Rick, P., Miller, V. "Identification of Klebsiella pneumoniae virulence determinants using an intranasal infection model". Molecular Microbiology. 2005. Volume 58, Issue 4. p. 1054–1073.

(6) Amako, K., Meno, Y., and Takade, A. "Fine Structures of the Capsules of Klebsiella pneumoniae and Escherichia coli K1". Journal of Bacteriology. 1988. Volume 170, No. 10. p. 4960-4962.

(7) Cortés, G., Borrell, N., de Astorza, B., Gómez, C., Sauleda, J., and Albertí, S. "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". Infection and Immunity. 2002. Volume 70, No. 5. p. 2583-2590.

(8) Friedlander C. Uber die scizomyceten bei der acuten fibrosen pneumonie. Arch Pathol Anat Physiol Klin Med 1882. 87:319-24.

(9) Hsueh CT, Chin JC, Yu YY, Chen HC, Li WC, Shen MC, Chiang CY, Shen SC. "Genetic analysis of the nitrogen fixation system in Klebsiella pneumoniae". Sci Sin. 1977. Volume 20, No. 6. p. 807-17.

(10) Espin G, Alvarez-Morales A, Merrick M. "Complementation analysis of glnA-linked mutations which affect nitrogen fixation in Klebsiella pneumoniae". Mol Gen Genet. 1981. Volume 184, No. 2. p. 213-7.

(11) Huang, H., Gong, CS., Tsao, GT. "Production of 1,3-propanediol by Klebsiella pneumoniae". Appl Biochem Biotechnol. 2002. 98-100:687-98.

(12)Brisse1, S., Milatovic1, D., Fluit, A. C., Verhoef, J. and Schmitz, F.-J. "Epidemiology of Quinolone Resistance of Klebsiella pneumoniae and Klebsiella oxytoca in Europe". European Journal of Clinical Microbiology & Infectious Diseases. 2000. Volume 19, Number 1. p. 64-68.

(13) Sylvain Brisse, Dana Milatovic, Ad C. Fluit, Jan Verhoef, Nele Martin, Sybille Scheuring, Karl Köhrer, and Franz-Josef Schmitz. "Comparative In Vitro Activities of Ciprofloxacin, Clinafloxacin, Gatifloxacin, Levofloxacin, Moxifloxacin, and Trovafloxacin against Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes Clinical Isolates with Alterations in GyrA and ParC Proteins." Antimicrobial Agents and Chemotherapy. 1999. Vol. 43, No. 8. p. 2051-2055.

(14) Victor L. Yu, Dennis S. Hansen, Wen Chien Ko, Asia Sagnimeni, Keith P. Klugman, Anne von Gottberg, Herman Goossens, Marilyn M. Wagener, and Vicente J. Benedi. "Virulence Characteristics of Klebsiella and Clinical Manifestations of K. pneumoniae Bloodstream Infections". Emerging Infectious Disease. 2007. Volume 13, Number 7.

(15) Cleggs, S. "Adherence of enterobacteria to eucaryotic receptors" 2007.

(16) Shinako Fukigaia, Jimena Albab, Soichiro Kimurab, Toshie Iidaa, Noriko Nishikuraa, Yoshikazu Ishiib, and Keizo Yamaguchi. "Nosocomial outbreak of genetically related IMP-1 β-lactamase-producing Klebsiella pneumoniae in a general hospital in Japan." International Journal of Antimicrobial Agents. 2007. Volume 29, Issue 3. p. 306-310

(17) Mohammed Benghezal, Eric Adam, Aurore Lucas, Christine Burn, Michael G. Orchard, Christine Deuschel, Emilio Valentino, Stéphanie Braillard, Jean-Pierre Paccaud, Pierre Cosson. "Inhibitors of bacterial virulence identified in a surrogate host model". 2007. Volume 9, Issue 5. p. 1336-1342.

(18) Wen-Chien Ko, David L. Paterson, Anthanasia J. Sagnimeni, Dennis S. Hansen, Anne Von Gottberg, Sunita Mohapatra, Jose Maria Casellas, Herman Goossens, Lutfiye Mulazimoglu, Gordon Trenholme, Keith P. Klugman, Joseph G. McCormack, and Victor L. Yu. "Community-Acquired Klebsiella pneumoniae Bacteremia: Global Differences in Clinical Patterns". 2002. Vol. 8, No. 2

(19) SUSANA MERINO, SILVIA CAMPRUBI, SEBASTIAN ALBERTI, VICENTE-JAVIER BENEDI, AND JUAN M. TOMAS. "Mechanisms of Klebsiella pneumoniae Resistance to Complement-Mediated Killing." 1992. INFECTION AND IMMUNITY. Vol. 60, No. 6. p. 2529-2535.

(20) NICOLE A CHRISTIAN, KAREN ROYE-GREEN, AND MONICA SMIKLE. "Molecular epiemiology of multidrug resistant extended spectrum beta-lactamase producing Klebsiella pneumoniae at a Jamaican hospital, 2000-2004." BMC Microbiology. 2010. Vol. 10, No. 27.

(21) Jang, S., Wheeler, L., Carey, R., Jensen, B., Crandall, C., Schrader, K., Jessup, D., Colegrove, K. and Gulland, F. "Pleuritis and suppurative pneumonia associated with a hypermucoviscosity phenotype of "Klebsiella pneumoniae" in California sea lions ("Zalophus californianus")." Veterinary Microbiology. 2010. Volume 141. p. 174-177.

Edited by Lauryn Samelko / Ashley Morawski, students of M Glogowski at Loyola University

Edited by James Tasch / Ani Michl (Loyola University Chicago)

Edited by Allyson Flores, student of Rachel Larsen

Edited by KLB