Klebsiella pneumoniae subsp. pneumoniae

The German microbiologist Carl Friedländer first described these bacteria as diplococci in 1883 as the causative agent of a rare form of pneumonia(Friedländer pneumonia). The genus Klebsiella is named after Edwin Klebs, a German bacteriologist.

Klebsiella pneumoniae subsp. pneumoniae are gram-negative, predominantly aerobic, facultatively anaerobic, sporeless, immobile rods surrounded by a mucus capsule (glycocalyx) . Typical of Klebsiella is a biofilm that forms on the colonies. Klebsiellae are chemoorganotrophs, i.e. they break down organic substances for energy production. In the oxic environment, they resort to oxidative energy metabolism. They oxidize organic substances to carbon dioxide and water. Under anoxic conditions, they use 2,3-butanediol fermentation for energy production.

The genus Klebsiella in the order Enterobacterales contains several species of human medical importance in the Enterobacteriaceae family. The species Klebsiella pneumoniae is additionally divided into 3 subspecies. This subdivision is based on characteristics of pathogenesis, but not on sufficient differentiation of the DNA sequence.

• Klebsiella pneumoniae subsp. ozaenae (Abel 1893); the pathogen is the cause of chronic atrophic rhinitis (ozaena)
• Klebsiella pneumoniae subsp. pneumoniae (Schroeter 1886)
• Klebsiella pneumoniae subsp. rhinoscleromatis (Trevisan 1887); the pathogen is the cause of rhinoscleroma, a granulomatous inflammation of the nasal mucosa.

Klebsiella species live in the soil, in water and on grain. Klebsiella pneumoniae is medically relevant as an inhabitant of the gastrointestinal tract. Klebsiella pneumoniae has the ability to survive in the intestine for a long time without causing symptoms. The bacterium is transmitted from person to person, but also via contact with contaminated surfaces. Its resilience, ability to multiply quickly and resistance to antibiotics make Klebsiella pneumoniae a real problem. Klebsiella pneumoniae is resistant to penicillin.

Alongside K. aerogenes, K. pneumoniae is particularly important as a pathogen for hospital-acquired infections, especially when it comes to multi-resistant bacterial strains.

Virulence factors: Klebsiella pneumoniae has several virulence factors:

• Capsule formation (glycocalyx): The capsule protects against phagocytosis and interferes with the complement system involved in the defense against microorganisms.
• Adhesins: They enable attachment to the host cells. Some Klebsiella pneumoniae adhesins also act as hemagglutinins.
• Fimbriae (pili): Formation of type 1 and type 3 fimbriae. Type 1 fimbriae attach to human epithelial cells (e.g. in the intestine or urinary tract). Type 3 fimbriae attach to endothelial cells, epithelial cells of the pulmonary alveoli and the urinary tract; furthermore to collagen type V.
• Lipopolysaccharides (LPS): LPS of the outer membrane act as antigens, the outward-facing polysaccharide chains are called O-antigens. Klebsiella pneumoniae expresses 9 different O-antigens, with O1 being the most common. The O antigens also interfere with the reaction cascade of the complement system.
• The bacterial siderophores are also important for pathogenicity. They serve to supply the cells with iron ions essential for metabolism by binding Fe3+ ions.
• Enterobactin: K. pneumoniae produces enterobactin (enterochelin), a toxin whose expression leads to a significantly increased virulence of the bacterium.

Klebsiella are facultative pathogens. About 3-5% of the population are carriers of Klebsiella pneumoniae - without becoming ill. However, people with a weakened immune system (premature babies) can become seriously ill. Infections vary greatly depending on where the bacterium colonizes. Klebsiella pneumoniae and Klebsiella oxytoca can cause pneumonia, lung abscesses, pleuritis, urinary tract infections, cholangitis, cholecystitis, meningitis, osteomyelitis, endocarditis, sepsis, peritonitis and intra-abdominal abscesses. Nosocomial outbreaks with multidrug-resistant Klebsiellae (also 4-MRGN) have been repeatedly described.

Germ detection is generally straightforward and is carried out exclusively by culture. Further differentiation can be carried out by checking the metabolic performance (so-called colored series) or using the MALDI-TOF method.

Klebsiella pneumoniae and autoimmune diseases: There are studies that indicate that IgA antibodiesdirected against Klebsiella pneumoniaecross-react with structures of the human cell surface protein HLA-B27. HLA-B27 regulates important functions of the human immune system. Klebsiella pneumoniae is also suspected of triggering autoimmune reactions such as ankylosing spondylitis (Bekhterev's disease) via this mechanism.

Klebsiella pneumoniae is naturally resistant to benzylpenicillin and aminobenzlypenicillins. In addition to this natural resistance, there are other acquired resistances that make treatment even more difficult. Tigecycline, polymyxins (e.g. colistin) and ceftazidime-avibactam have the highest in-vitro activity. Relebactam, an intravenously administered inhibitor of class A and C beta-lactamases, is recommended if the pathogen develops widespread resistance.

Resistance: The increasing resistance of Klebsiella pneumoniae worldwide is mainly induced by plasmid-encoded ESBL and carbapenemases. The highest prevalence is found in Eastern Europe and Asia as well as in nosocomial isolates. The prevalence of resistance to fluoroquinolones and ESBL strains is approx. 17% in Germany. The resistance rate to meropenem is 1-2 %. Approximately 6% of all strains show combined resistance to quinolones, 3rd generation cephalosporins and aminoglycosides; in Europe, the average is 20.5% (as of 2020).

1. Russo TA et al (2019) Hypervirulent Klebsiella pneumoniae. Clin Microbiol Rev. 32:e00001-19.
2. Siu LK et al (2012) Klebsiella pneumoniae liver abscess: a new invasive syndrome. Lancet Infect Dis 12:881-887.
3. Wyres KL et al (2020) Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol 18: 344-359.
4. Xu L et al (2017) Systematic review and meta-analysis of mortality ofpatients infected with carbapenem-resistant Klebsiella pneumoniae. Ann Clin Microbiol Antimicrob 16:18. doi: 10.1186/s12941-017-0191-3.
5. Zhang L et al. (2018) The association of HLA-B27 and Klebsiella pneumoniae in ankylosing spondylitis: A systematic review. Microb Pathog 117:49-54.