Abstract
Klebsiella pneumoniae successfully colonizes host tissues by recognizing and interacting with cholesterol present on membrane-associated lipid rafts. In this study, we evaluated the role of cholesterol in the expression of capsule polysaccharide genes of K. pneumoniae and its implication in resistance to phagocytosis. Our data revealed that exogenous cholesterol added to K. pneumoniae increases macrophage-mediated phagocytosis. To explain this event, the expression of capsular galF, wzi, and manC genes was determined in the presence of cholesterol. Down-regulation of these capsular genes occurred leading to increased susceptibility to phagocytosis by macrophages. In contrast, depletion of cholesterol from macrophage membranes led to enhanced expression of galF, wzi, and manC genes and to capsule production resulting in resistance to macrophage-mediated phagocytosis. Cholesterol-mediated repression of capsular genes was dependent on the RcsA and H-NS global regulators. Finally, cholesterol also down-regulated the expression of genes responsible for LPS core oligosaccharides production and OMPs. Our results suggest that cholesterol plays an important role for the host by reducing the anti-phagocytic properties of the K. pneumoniae capsule facilitating bacterial engulfment by macrophages during the bacteria-eukaryotic cell interaction mediated by lipid rafts.
Highlights
Klebsiella pneumoniae is an opportunistic Gram-negative rodshaped bacterium belonging to the Enterobacteriaceae family that predominantly affects patients with a compromised immune system and is one of the most prevalent causes of nosocomial infections, such as pneumonia, urinary tract infections, meningitis, necrotizing fasciitis, endophthalmitis, pyogenic liver abscess, and sepsis (Podschun and Ullmann, 1998; AlcantarCuriel and Giron, 2015)
K. pneumoniae expresses different virulence factors such as capsule, fimbriae, lipolysaccharide (LPS) and outer membrane proteins (OMPs) (Podschun and Ullmann, 1998). fimA, mrkA, and ecpA genes code for the major pilin subunits of type I, type III, and ECP fimbria, which are involved in the adherence to epithelial cells and formation of biofilms (Struve et al, 2009; AlcantarCuriel et al, 2013)
To evaluate the effect of cholesterol on the expression of the capsule polysaccharide, K. pneumoniae was grown in Lysogeny Broth (LB) in absence and in presence of cholesterol
Summary
Klebsiella pneumoniae is an opportunistic Gram-negative rodshaped bacterium belonging to the Enterobacteriaceae family that predominantly affects patients with a compromised immune system and is one of the most prevalent causes of nosocomial infections, such as pneumonia, urinary tract infections, meningitis, necrotizing fasciitis, endophthalmitis, pyogenic liver abscess, and sepsis (Podschun and Ullmann, 1998; AlcantarCuriel and Giron, 2015). K. pneumoniae requires the presence of lipid rafts located on the macrophages membrane and cholesterol plays an important role in this interaction enhancing phagocytosis (Huang et al, 2013; Cano et al, 2015). This cholesterol-rich microenvironment could affect the expression of virulence factors including capsule. The presence of cholesterol negatively affected the expression of the three operons that code for capsule polysaccharide, enhancing macrophage-mediated phagocytosis. In addition to capsule polysaccharide, cholesterol repressed the expression of genes that code for both the lipopolysaccharide core and the outer membrane proteins. Our data show that cholesterol exerts a negative effect on the expression of K. pneumoniae virulence factors
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