Klebsiella pneumoniae

What type of bacteria is Klebsiella and where is it usually required?

• Gram -ve

• Nosocomial infections

What is the Mortality rate of Klebsiella infection?

20-40% mortality rate

What are the virulence factors of K. pneumoniae?

• Polysaccharide capsule (K antigen)

• LPS

• Siderophores

• Biofilms and Adhesin

How does the Polysaccharide capsule contribute to virulence?

• Virulence is seen with increased capsule production mediated by

• Immune evasion preventing phagocytosis, complement depostion, Opsonisation

• Involved in biofilm formation

How does LPS contribute to virulence?

Endotoxin composed of Lipid A, O-antigen and oligosaccharide core. Upon bacterial lysis or death, Lipid A is released.

• Lipid A binds to TLR4 triggering pro-inflammatory cytokine production (TNF-alpha, IL-1, IL-6). If dysregulated leads to excessive damaging inflammation leading to vascular leakage, clotting abnormalities and tissue hypoperfusion

• LPS is barrier to complement and antibodies

• Can evade immune by altering O antigen structure

How do Sideophores contribute to virulence?

Iron is important for pathogenesis and are competitive resources

• K. pneumoniae has a range of Sideophores: enterobactin, aerobactin, yersinobactin, salmochelin

• Siderophroes can bind Fe with very high affinity outcompeting host sequestering proteins like Lactoferrin

• Scavenge Iron from the limited host environment, counteracting host nutruitinal immunity

Importance of Iron?

• Electron transport (respiration)

• DNA synthesis

• Metabolic enzymes

What is the importance of Adhesin/Type I fimbriae

Allow attachment of biotic factors and abiotic surfaces allowing colonisation and biofilm formation

What are the multi-drug resistance mechanisms of Klebsiella pneumoniae?

• Beta-lactamases

• Decreased cell permability due to loss of Omps

• Modification Antibiotic targets

• Efflux pumps

How is Klebsiella resistant to Carbapenem

Carbepenemases - e.g. New Dehli metallo-beta-lactamase

• Zinc metalloprotein that hydrolyses the Beta-lactam ring

  Efflux pump

• AcrAB-TolC - AcrB actively pumps out Drugs vis proton motive force, AcrA acts as an adaptor proteins and TolC is a channel that allows exit

  Loss of porins

• OmpK36 and OmpK35