AUTHOR=Ares Miguel A. , Sansabas Alejandro , Rodríguez-Valverde Diana , Siqueiros-Cendón Tania , Rascón-Cruz Quintín , Rosales-Reyes Roberto , Jarillo-Quijada Ma. Dolores , Alcántar-Curiel María D. , Cedillo María L. , Torres Javier , Girón Jorge A. , De la Cruz Miguel A. 

TITLE=The Interaction of Klebsiella pneumoniae With Lipid Rafts-Associated Cholesterol Increases Macrophage-Mediated Phagocytosis Due to Down Regulation of the Capsule Polysaccharide

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2019.00255

DOI=10.3389/fcimb.2019.00255

ISSN=2235-2988

ABSTRACT=<p><italic>Klebsiella pneumoniae</italic> 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 <italic>K. pneumoniae</italic> and its implication in resistance to phagocytosis. Our data revealed that exogenous cholesterol added to <italic>K. pneumoniae</italic> increases macrophage-mediated phagocytosis. To explain this event, the expression of capsular <italic>galF, wzi</italic>, and <italic>manC</italic> 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 <italic>galF, wzi</italic>, and <italic>manC</italic> 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 <italic>K. pneumoniae</italic> capsule facilitating bacterial engulfment by macrophages during the bacteria-eukaryotic cell interaction mediated by lipid rafts.</p>