Klebsiella pneumoniae triggers a cytotoxic effect on airway epithelia
Klebsiella pneumoniae is the most common Gram-negative bacterium causing community acquired pneumonia and up to 5% of community-acquired urinary tract infections. Community-acquired pneumonia is a very severe illness with a rapid onset, and despite the availability of an adequate antibiotic regimen, the outcome is often fatal. The observed mortality rates are about 50%. Capsule polysaccharide (CPS), siderophores, lipopolysaccharide (LPS) and adhesins are virulence factors identified for this pathogen. However, most of the studies have focused on the role of CPS in Klebsiella virulence. Early studies suggested that an extracellular toxic complex mainly composed of CPS triggers extensive lung tissue damage and data indicate that there might be a correlation between the production of this extracellular complex and Klebsiella virulence. Similar to CPSs from other pathogens, Klebsiella CPS is responsible for resistance to complement mediated killing and impedes adhesion to and invasion of epithelial cells by sterically preventing receptor-target recognition of bacterial adhesins. Recently it has been demonstrated that CPS mediates resistance to antimicrobial peptides (APs), trapping APs and thus acting as a bacterial decoy. This study shows that K. pneumoniae triggers a cytotoxic effect upon infection of human lung epithelial cells. This process requires the presence of capsulated live bacteria through the time of infection.
Klebsiella pneumoniae triggers a cytotoxic effect on airway epithelial cells. 2009 BMC Microbiology 9: 156 doi:10.1186/1471-2180-9-156
Klebsiella pneumoniae is a capsulated Gram negative bacterial pathogen and a frequent cause of nosocomial infections. Despite its clinical relevance, little is known about the features of the interaction between K. pneumoniae and lung epithelial cells on a cellular level, neither about the role of capsule polysaccharide, one of its best characterised virulence factors, in this interaction. The interaction between Klebsiella pneumoniae and cultured airway epithelial cells was analysed. K. pneumoniae infection triggered cytotoxicity, evident by cell rounding and detachment from the substrate. This effect required the presence of live bacteria and of capsule polysaccharide, since it was observed with isolates expressing different amounts of capsule and/or different serotypes but not with non-capsulated bacteria. Cytotoxicity was analysed by lactate dehydrogenase and formazan measurements, ethidium bromide uptake and analysis of DNA integrity, obtaining consistent and complementary results. Moreover, cytotoxicity of non-capsulated strains was restored by addition of purified capsule during infection. While a non-capsulated strain was avirulent in a mouse infection model, capsulated K. pneumoniae isolates displayed different degrees of virulence. Our observations allocate a novel role to K. pneumoniae capsule in promotion of cytotoxicity. Although this effect is likely to be associated with virulence, strains expressing different capsule levels were not equally virulent. This fact suggests the existance of other bacterial requirements for virulence, together with capsule polysaccharide.
Tags: Bacteria, Biology, Emerging disease, Health, Klebsiella, Medicine, Microbiology, Science
