Journal of Biological Chemistry
Volume 286, Issue 44, 4 November 2011, Pages 38211-38219
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Microbiology
Apolipoprotein A-I Exerts Bactericidal Activity against Yersinia enterocolitica Serotype O:3*

https://doi.org/10.1074/jbc.M111.249482Get rights and content
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Apolipoprotein A-I (apoA-I), the main protein component of high density lipoprotein (HDL), is well recognized for its antiatherogenic, antioxidant, and antiinflammatory properties. Here, we report a novel role for apoA-I as a host defense molecule that contributes to the complement-mediated killing of an important gastrointestinal pathogen, Gram-negative bacterium Yersinia enterocolitica. We specifically show that the C-terminal domain of apoA-I is the effector site providing the bactericidal activity. Although the presence of the lipopolysaccharide O-antigen on the bacterial surface is absolutely required for apoA-I to kill the bacteria, apoA-I does not interact with the bacteria directly. To the contrary, exposure of the bacteria by serum proteins triggers apoA-I deposition on the bacterial surface. As our data show that both purified lipid-free and HDL-associated apoA-I displays anti-bacterial potential, apoA-I mimetic peptides may be a promising therapeutic agent for the treatment of certain Gram-negative infections.

Apolipoproteins
Bacteria
Complement
High Density Lipoprotein (HDL)
Lipopolysaccharide (LPS)
Innate Immunity

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*

This work was supported, in whole or in part, by National Institutes of Health Grant HL48739 (to V. Z.). This work was also supported by the Finnish Cultural Foundation (to M. B.-S.), the Paulo Foundation (to M. B.-S.), the Aarne Koskelon Foundation (to M. B.-S.), Orion Farmos (to M. B.-S.), the Alfred Kordelin Foundation (to M. B.-S.), the Research Council for Biosciences and Environment, Academy of Finland Grant 114075 (to M. S.), the Finnish Foundation for Cardiovascular Research (to M. J.), and the Research Council for Health, Academy of Finland, Grant 132629 (to M. J.).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1 and 2, Table 1, Methods, and additional references.